Apparatus and method to treat a disease process in a luminal structure

ABSTRACT

An apparatus and a method to treat a disease process in a luminal structure. A dual-balloon catheter for treating a disease process in a luminal structure of a patient comprises an inner balloon, an outer balloon substantially concentric with and substantially surrounding the inner balloon, an inner balloon fluid delivery lumen in fluid connection with the inner balloon, and an outer balloon fluid delivery lumen in fluid connection with the outer balloon.

[0001] This application is a continuation-in-part of pending applicationSer. No. 08/565,093, filed Nov. 30, 1995, which is acontinuation-in-part of application Ser. No. 08/184,380, filed Jan. 21,1994, now U.S. Pat. No. 5,503,613, issued Apr. 2, 1996.

BACKGROUND OF THE INVENTION

[0002] The present invention relates to an apparatus and a method totreat a disease process in a luminal structure. Such a structureincludes, but is not limited to, veins, arteries, bypass graftprostheses, the gastrointestinal (GI) tract, the biliary tract, thegenitourinary (GU) tract, and the respiratory tract (e.g. thetracheobronchial tree).

[0003] Within this application several publications are referenced byArabic numerals within parentheses. Full citations for these referencesmay be found at the end of the specification immediately preceding theclaims. The disclosures of all of these publications in their entiretiesare hereby incorporated by reference into this application in order tomore fully describe the state of the art to which this inventionpertains.

[0004] Percutaneous transluminal coronary angioplasty (“PCTA”) iscommonly used in the treatment of coronary artery obstruction, with over400,000 procedures performed annually. The process involves theinsertion of balloon catheters through the femoral artery to thetargeted coronary artery. Injection of radio-opaque contrast into theproximal coronary artery allows fluoroscopic localization of stenosedcoronary segments. Balloon catheters are advanced to the site ofstenosis over extremely thin guide wires to position the catheter at thepoint of occlusion. The distal end of the catheter contains a balloonwhich is inflated for 2-4 minutes to the full diameter of the occludedartery, decreasing the blockage and improving blood flow.

[0005] Approximately 40% of patients undergoing this procedure haveangiographic evidence of restenosis by 12 months. The biologicalprocesses responsible for restenosis are not fully understood, butappear to result from abnormal proliferation of the “insulted” smoothmuscle cells and neointima formation in the segment of treated artery(6). Although coronary artery blockage is a non-malignant disease, ithas been suggested that treatment of the internal vessel walls withionizing radiation could inhibit cell growth, and delay or even preventrestenosis (4, 7, 10-13).

[0006] As stated above, restenosis after arterial intervention ingeneral, PTCA in particular, seem to be primarily due to medial smoothmuscle cell proliferation. Conventional PTCA is performed using aballoon catheter such an over-the-wire type catheter manufactured, forexample, by Scimed Life Systems, Inc, of Maple Grove, Minn. or amono-rail type catheter manufactured, for example, by AdvancedCardiovascular Systems, Inc, of Temecula, Calif. FIG. 1 depicts such aconventional over-the-wire balloon catheter 1. The conventional ballooncatheter 1 is utilized in an angioplasty procedure as follows. Aconventional guidewire 2 is inserted into the patient's artery until thedistal end of the guidewire 2 is past a target area (not shown) of theartery (not shown) where there is a buildup of material. Theconventional balloon catheter 1 has a lumen 3 running therethrough. Theguidewire 2 is inserted into the distal end of the balloon catheter 1and the balloon catheter 1 is advanced over the guidewire until theballoon section 1 a of the balloon catheter 1 is adjacent the buildup ofmaterial. The balloon section 1 a is then inflated by an inflation means(not show) connected to an inflation port 1 b to clear the artery.Finally, the balloon section 1 a is deflated, the balloon catheter 1 ispulled back up the guidewire and removed and the guidewire is likewiseremoved from the patient's artery.

[0007] Current technology contemplates two distinct design classes fordevices for the prevention of restenosis after arterial interventions.The first design class, an arterial stent type device, is designed forlong term deployment within the artery. Such a stent, if designed toemit radiation, would be in place long after the time necessary for theprevention of smooth muscle cell proliferation at the arterial site.U.S. Pat. No. 5,059,166 to Fischell describes such a long term stent.

[0008] The second design class for restenosis preventing devicescontemplates the delivery of unspecified doses of radiation viaradioactive catheters and guidewires. These devices utilize a movable,flexible radiation shield. However, it is questionable whether such aradiation shield could be constructed given the thickness of materialrequired to shield the radiation source and the flexibility required toallow delivery of the radiation source and shield to the coronary site.U.S. Pat. No. 5,213,561 to Weinstein relates to a device of this class.

[0009] In addition, neither class of devices addresses the need toisolate the radioactive source from contact with the patient's bodyfluids.

[0010] In a related area, brachytherapy involves the placement of aradioactive source within tissue to deliver localized radiation and isfrequently applied to treat recurrent disease in an area previouslytreated by external beam radiation. Blind-end catheters may be used todeliver radiation to tumors in the esophagus, trachea, or rectum, forexample. Advantages include the sparing of critical structures close tothe tumor, and brevity of treatment (hours to days). Difficultiesprimarily involve anatomic constrains on implant placement. Commonapplications include the endoluminal treatment of recurrentendobronchial and bile duct tumors, the intracavitary treatment ofcervical and endometrial cancer, and interstitial implants inunrespectable tumors with catheters or radioactive seeds.

SUMMARY OF THE INVENTION

[0011] It is an object of the present invention to provide anarrangement for reducing restenosis after arterial or vascularintervention in a patient. Such intervention includes, but is notlimited to, balloon angioplasty, atherectomy, stent placement, arterialgrafts, and arteriovenous fistula.

[0012] Moreover, it is noted that long term hemodialysis therapy iscomplicated by thrombosis of both hemodialysis grafts and native shunts.Late graft failure (after about 6 weeks) is commonly associated withanatomic stenosis at the venous anastomosis, within the graft, or moreproximally in the central venous system. Irradiation of theproliferative tissue from an intravascular source will inhibit thedevelopment of shunt outflow stenosis and thus decrease the incidence ofthrombosis from the ensuing low flow state. Any proliferative tissue atthe site of a vascular graft would also be amenable to this treatment.

[0013] It is a further object of the present invention to provide anarrangement for reducing restenosis after vascular intervention in thepatient by delivering a precise dosage of radiation to the patient'sartery at a target area.

[0014] It is a further object of the present invention to provide anarrangement for reducing restenosis after vascular intervention in thepatient by delivering precise radioactive dosage to the patient's arteryat a target area while eliminating contact between the radioactivesource and the patient's body fluids.

[0015] It is a further object of the present invention to provide anarrangement for reducing restenosis after vascular intervention in thepatient by delivering a precise radioactive dosage to the patient'sartery at a target area while shielding a doctor and other staff fromover-exposure to radiation.

[0016] It is another object of the present invention to provide anarrangement and method for treating a disease process or processes in aluminal structure or structures. Such structure or structures include,but are not limited to, veins, arteries, bypass graft prostheses, thegastrointestinal (GI) tract, the biliary tract, the genitourinary (GU)tract, and the respiratory tract (e.g. the tracheobronchial tree). Thediseases to be treated by the invention include proliferative diseases(both malignant and non-malignant).

[0017] According to one aspect of the present invention, an apparatusguided by a guidewire within a patient's artery for reducing restenosisafter arterial intervention in the patient's artery is provided,comprising a radiation dose delivery wire with a radiation sourceencapsulated within its distal end, and a balloon catheter with a blindlumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire, said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0018] According to another aspect of the present invention, anapparatus inserted into a sheath in a patent's artery and guided by aguidewire within the patient's artery for reducing restenosis afterarterial intervention in the patient's artery is provided, comprising aradiation dose delivery wire with a radiation source encapsulated withinits distal end, and a balloon catheter with a blind lumen sealed at itsdistal end and a guidewire lumen extending therethrough to accept saidguidewire, said blind lumen being adapted to accept said radiation dosedelivery wire into its proximal end, said balloon catheter being adaptedto be inserted into said sheath.

[0019] According to another aspect of the present invention, anapparatus guided by a guidewire within a patient's artery for reducingrestenosis after arterial intervention in the patient's artery isprovided, comprising a radiation dose delivery wire with a radiationsource encapsulated within its distal end, and a balloon catheter with ablind lumen sealed at its distal end and a guidewire lumen extendingpartially through said balloon catheter, said blind lumen being adaptedto accept said radiation dose delivery wire into its proximal end, saidguidewire lumen having an entry port located at a distal end of saidballoon catheter and an exit port located upon a circumferential surfaceof said balloon catheter.

[0020] According to another aspect of the present invention, anapparatus for reducing restenosis after arterial intervention in apatient's-artery is provided, comprising a guidewire for insertion intothe patient's artery at least as far as a target area of the artery, aradiation dose delivery wire with a radiation source encapsulated withinits distal end, and a balloon catheter with a blind lumen sealed at itsdistal end and a guidewire lumen extending therethrough to accept saidguidewire, said blind lumen being adapted to accept said radiationdelivery wire into its proximal end.

[0021] According to another aspect of the present invention, anapparatus guided by a guidewire within a patient's artery for reducingrestenosis after arterial intervention in the patient's artery isprovided, comprising a radiation dose delivery wire with a radiationsource encapsulated within its distal end, and a catheter with a blindlumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire, said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0022] According to another aspect of the present invention, anapparatus to be inserted into a catheter for reducing restenosis afterarterial intervention in a patient's artery is provided, comprising aradiation dose delivery wire with a radiation source encapsulated withinits distal end, and a blind lumen open at its proximal end and sealed atits distal end, said blind lumen being adapted to accept said radiationdose delivery wire into its proximal end and to be inserted into saidcatheter.

[0023] According to another aspect of the present invention, a method ofreducing restenosis after arterial intervention in a patient's artery isprovided, comprising inserting a guidewire into the patient's arteryuntil a distal end of the guidewire is at least as far into the arteryas a predetermined section of the artery, inserting the guidewire into aguidewire lumen of a balloon catheter with a blind lumen, inserting theballoon catheter with the blind lumen into the patient's artery at leastas far as the predetermined section of the artery, inserting a radiationdose delivery wire into said blind lumen in said balloon catheter,moving said radiation dose delivery wire a predetermined distance intothe blind lumen of the balloon catheter for a predetermined period oftime, and removing said radiation dose delivery wire from said blindlumen of said balloon catheter after said predetermined period of time.

[0024] According to another aspect of the instant invention an apparatusfor use with a guidewire for reducing restenosis after arterialintervention in a patient's artery is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's artery,said balloon catheter having a radiation producing coating on aninternal surface.

[0025] The radiation producing coating may include a material selectedfrom the group consisting of Al-26, Sn-123, K-40, Sr-89, Y-91, Ir-192,Cd-115, P-32, Rb-86, I-125, Pd-103, and Sr-90, or any other materialselected from Table 2, for example.

[0026] Regarding Tables 2-4, it is noted that the legend “A” refers toatomic mass, the half-life is given in years, days, hours, and minutes,where appropriate, a “Rad. Type” (radiation type) B+ indicates emissionof a positron particle, B− indicates the emission of a beta particle,and G indicates the emission of a gamma photon.

[0027] The radiation producing coating may comprise a lacquer, a glue,an acrylic, or a vinyl.

[0028] The balloon portion of the catheter may be formed of a plasticmaterial such as polyethylene, PET, and nylon.

[0029] According to another aspect of the instant invention an apparatusfor use with a guidewire for reducing restenosis after arterialintervention in a patient's artery is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's artery,said balloon catheter having a radiation producing coating on anexterior surface.

[0030] The radiation producing coating may include a material selectedfrom the group consisting of Al-26, Sn-123, K-40, Sr-89, Y-91, Ir-192,Cd-115, P-32, Rb-86, I-125, Pd-103, and Sr-90, or any other materialselected from Table 2, for example.

[0031] The radiation producing coating may comprise a lacquer, a glue,an acrylic, or a vinyl.

[0032] The balloon catheter may be formed of a plastic material chosenfrom the group consisting of polyethylene, PET, and nylon.

[0033] According to another aspect of the instant invention an apparatusfor use with a guidewire for reducing restenosis after arterialintervention in a patient's artery is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's artery,said balloon catheter being formed of a flexible material including aradiation producing source.

[0034] The flexible material may be formed of a plastic material such aspolyethylene, PET, and nylon.

[0035] The plastic material may be doped with said radiation producingsource.

[0036] The radiation producing source may be chemically bonded to saidplastic material by a covalent bond.

[0037] The radiation producing source may be bonded to said plasticmaterial by an ionic bond.

[0038] The radiation producing source may be bonded to said plasticmaterial by a biotin-avidin link.

[0039] The radiation producing source may be bonded to said plasticmaterial by coextrusion.

[0040] According to another aspect of the instant invention a method forreducing restenosis after arterial intervention in a patient's artery isprovided, comprising inserting a balloon catheter with a fluid deliveryport connected thereto into the patient's artery and inserting aradioactive fluid into the balloon catheter through the fluid deliveryport.

[0041] The radioactive fluid may be selected from the group consistingof fluids containing Cu-61, Se-73, Co-55, Sc-44, Sr-75, Kr-77, Ga-68,In-110, Br-76, Ga-66, Ga-72, Sb-122, Na-24, Si-31, Ge-77, Ho-166,Re-188, Bi-212, Y-90, K-42, Ir-192, I-125, Pd-103, Sr-90, andradioactive sodium-chloride, or any other chemical compound formulatedfrom the isotopes given in Table 3, for example.

[0042] According to another aspect of the instant invention an apparatusguided by a guidewire within a patient's artery for receiving aradiation dose delivery wire with a radiation source encapsulated withinits distal end and for reducing restenosis after arterial interventionin the patient's artery is provided, comprising a balloon catheter witha blind lumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire, said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0043] According to another aspect of the present invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; aballoon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending therethrough to accept said guidewire; saidblind lumen being adapted to accept said radiation delivery wire intoits proximal end; and means for moving the distal end of said radiationdose delivery wire to a predetermined position within said blind lumenfor a predetermined period of time.

[0044] According to another aspect of the present invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; aballoon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending therethrough to accept said guidewire; saidblind lumen being adapted to accept said radiation dose delivery wireinto its proximal end; and a radiation blocking shield movable betweenthe radiation source within the patient's luminal structure and a userof the apparatus.

[0045] According to another aspect of the instant invention an apparatusinserted into a sheath in a luminal structure of a patient and guided bya guidewire within the patient's luminal structure for treating adisease process is provided, comprising a radiation dose delivery wirewith a radiation source attached to its distal end; a balloon catheterwith a blind lumen sealed at its distal end and a guidewire lumenextending therethrough to accept said guidewire; said blind lumen beingadapted to accept said radiation dose delivery wire into its proximalend; said balloon catheter being adapted to be inserted into saidsheath; and means for providing a liquid-tight seal between theradiation dose delivery wire and the proximal end of the blind lumen.

[0046] According to another aspect of the instant invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; and aballoon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending partially through said balloon catheter; saidblind lumen being adapted to accept said radiation dose delivery wireinto its proximal end; said guidewire lumen having an entry port locatedat a distal end of said balloon catheter and an exit port located upon acircumferential surface of said balloon catheter.

[0047] According to another aspect of the instant invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; and acatheter with a blind lumen sealed at its distal end and a guidewirelumen extending therethrough to accept said guidewire; said blind lumenbeing adapted to accept said radiation dose delivery wire into itsproximal end.

[0048] According to another aspect of the instant invention an apparatuswith a catheter to be inserted into a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; and ablind lumen open at its proximal end and sealed at its distal end; saidblind lumen being adapted to accept said radiation dose delivery wireinto its proximal end and to be inserted into said catheter.

[0049] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted in a luminal structure of a patientfor treating a disease process is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's luminalstructure; said balloon catheter having a radiation producing coating onan internal surface.

[0050] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted into a luminal structure of a patientfor treating a disease process is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's luminalstructure; said balloon catheter having a radiation producing coating onan exterior surface.

[0051] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted into a luminal structure of a patientfor treating a disease process is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's luminalstructure; said balloon catheter being formed of a flexible materialincluding a radiation producing source.

[0052] According to another aspect of the instant invention a method fortreating a disease process in a luminal structure of a patient isprovided, comprising inserting a balloon catheter with a fluid deliveryport connected thereto into the patient's artery; inserting aradioactive fluid into the balloon catheter through the fluid deliveryport.

[0053] According to another aspect of the instant invention an apparatusguided by a guidewire within a luminal structure of a patient forreceiving a radiation dose delivery wire with a radiation source on itsdistal end and for treating a disease process is provided, comprising aballoon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending therethrough to accept said guidewire; saidblind lumen being adapted to accept said radiation delivery wire intoits proximal end.

[0054] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted into a luminal structure of a patientfor treating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; and aballoon catheter with a blind lumen sealed at its distal end a guidewirelumen extending therethrough adapted to accept a guidewire for guidingthe balloon catheter in the patient's luminal structure; said blindlumen being adapted to accept said radiation dose delivery wire into itsproximal end.

[0055] According to another aspect of the instant invention an apparatusfor use with a sheath and a guidewire inserted into a luminal structureof a patient for treating a disease process is provided, comprising aradiation dose delivery wire with a radiation source attached to itsdistal end; and a balloon catheter with a blind lumen sealed at itsdistal end and a guidewire lumen extending therethrough adapted toaccept a guidewire for guiding the balloon catheter in the patient'sluminal structure; said blind lumen being adapted to accept saidradiation dose delivery wire into its proximal end; said ballooncatheter being adapted to be inserted into a sheath in the patient'sluminal structure surrounding said guidewire.

[0056] According to another aspect of the instant invention an apparatusinserted into a luminal structure of a patient for treating a diseaseprocess is provided, comprising a guidewire for insertion into thepatient's luminal structure at least as far as a target area of theluminal structure; a radiation dose delivery wire with a radiationsource attached to its distal end; and a balloon catheter with a blindlumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire; said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0057] According to another aspect of the instant invention a method oftreating a disease process in a patient is provided, comprisinginserting a guidewire into a luminal structure of the patient until adistal end of the guidewire is at least as far into the luminalstructure as a predetermined section of the luminal structure; insertingthe guidewire into a guidewire lumen of a balloon catheter with a blindlumen; inserting the balloon catheter with the blind lumen into thepatient's luminal structure at least as far as the predetermined sectionof the luminal structure; inserting a radiation dose delivery wire intosaid blind lumen in said balloon catheter; moving said radiation dosedelivery wire into said blind lumen in said balloon catheter; movingsaid radiation dose delivery wire a predetermined distance into theblind lumen of the balloon catheter for a predetermined period of time;and removing said radiation dose delivery wire from said blind lumen ofsaid balloon catheter after said predetermined period of time.

[0058] According to another aspect of the instant invention a method forreducing restenosis after arterial intervention in a patient's artery isprovided, comprising inserting a balloon catheter with a fluid deliveryport connected thereto into the patient's artery, and inserting aradioactive fluid into the balloon catheter through the fluid deliveryport, said radioactive fluid being selected from the group consisting ofradioisotopes that decay with emission of beta plus or beta minusradiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in % perdecay. The radioisotopes may be non-iodine and non-phosphorus based.

[0059] According to another aspect of the instant invention an apparatusfor reducing restenosis after arterial intervention in a patient'sartery is provided, comprising a balloon catheter with a fluid deliveryport connected thereto, and a radioactive fluid inserted into theballoon catheter through the fluid delivery port, said radioactive fluidbeing selected from the group consisting of radioisotopes that decaywith emission of beta plus or beta minus radiation, that have ahalf-life of between approximately 1 and 72 hours, that have an averagedecay energy of approximately 500-2000 keV, and that have radiationintensity of greater than or equal to approximately 50%, said radiationintensity being measured in % per decay. The radioisotopes may benon-iodine and non-phosphorus based.

[0060] According to another aspect of the instant invention adual-balloon catheter for treating a disease process in a luminalstructure of a patient is provided, comprising an inner balloon, anouter balloon substantially concentric with and substantiallysurrounding the inner balloon, an inner balloon fluid delivery lumen influid connection with the inner balloon, and an outer balloon fluiddelivery lumen in fluid connection with the outer balloon.

[0061] According to another aspect of the instant invention a method fortreating a disease process in a luminal structure of a patient isprovided, comprising inserting into the luminal structure a dual-ballooncatheter including an inner balloon, an outer balloon substantiallyconcentric with and substantially surrounding the inner balloon, aninner balloon fluid delivery lumen in fluid connection with the innerballoon, and an outer balloon fluid delivery lumen in fluid connectionwith the outer balloon, and inserting a radioactive fluid into at leastone of the inner balloon and the outer balloon through the inner balloonfluid delivery lumen and the outer balloon fluid delivery lumen,respectively.

[0062] According to another aspect of the instant invention anindiflator for inserting fluid into a balloon catheter is provided,comprising an elongated tube for holding the fluid, the elongated tubehaving a first end and a second end, the first end of the elongated tubehaving a wall across the tube with a port therein for providing a fluidpassage between an interior of the tube and an exterior of the tube, aplunger assembly including a plunger head with a first face and a secondface and a plunger stem having first and second ends, the plunger headbeing adapted to slide within the tube and being connected to the firstend of the plunger stem, lock means disposed at the second end of thetube for accepting and releasably locking the plunger stem, the secondend of the plunger stem being disposed outside the tube, and a pressurevalve disposed adjacent the second end of the plunger stem and beingoperatively connected to a pressure transducer on the second face of theplunger head facing the first end of the tube, whereby the pressurevalve displays a pressure in an area of the tube between the first endof the tube and the second face of the plunger head.

[0063] These and other advantages will become apparent from the detaileddescription, accompanying the claims and attached drawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0064]FIG. 1 shows the construction of a conventional over-the-rail typeballoon catheter;

[0065]FIG. 2, shows the construction of a balloon catheter according toa first embodiment of the present invention;

[0066]FIG. 3 shows a cross-section of the balloon catheter according tothe first embodiment of the present invention;

[0067]FIG. 4 shows the construction of a radiation dose delivery wire ofthe present invention;

[0068]FIG. 5 shows the construction of a second embodiment of thepresent invention;

[0069]FIG. 6 shows the construction of a third embodiment of the presentinvention;

[0070]FIG. 7 shows the construction of a fourth embodiment of thepresent invention;

[0071]FIG. 8 shows the construction of a fifth embodiment of the presentinvention;

[0072]FIG. 9 shows the construction of a sixth embodiment of the presentinvention;

[0073]FIG. 10 shows the construction of a seventh embodiment of thepresent invention;

[0074]FIG. 11 shows dose versus distance for Ir-192, I-125, Pd-103,P-32, and Sr-90;

[0075]FIG. 12 shows dose asymmetry (defined as maximum/minimum dose tovessel wall) resulting from inaccurate centering of 5 mm long P-32,Sr-90, or Ir-192 sources within arteries of 3 and 5 mm diameter;

[0076]FIG. 13 shows a comparison of dose asymmetry for Sr-90 and Ir-192sources of 5 and 30 mm length in a 3 mm diameter vessel;

[0077]FIG. 14 shows radial dose distribution for P-32 wires of 0.65 and1.3 mm diameter, and for a 3 mm diameter P-32 balloon;

[0078]FIG. 15 shows the construction of a radiation dose delivery wirein another embodiment of the present invention;

[0079]FIG. 16 shows the construction of a radiation dose delivery wirein yet another embodiment of the present invention;

[0080]FIG. 17 shows a cross-section of a dual-balloon catheter accordingto another embodiment of the present invention;

[0081]FIG. 18 shows a cross-section of an indiflator according to anembodiment of the invention for use with a balloon catheter;

[0082]FIG. 19 shows the cross-section of a shield for use with theindiflator of FIG. 18;

[0083]FIG. 20 shows a cross-section of a lumen according to anembodiment of the invention for use with a balloon catheter;

[0084]FIG. 21 shows a schematic drawing of a 3-way stopcock according toan embodiment of the invention for use with an indiflator and a ballooncatheter;

[0085]FIG. 22 shows a case for a 3-way stopcock according to anembodiment of the invention for use with an indiflator and a ballooncatheter;

[0086]FIG. 23 shows a container according to an embodiment of theinvention for holding a radioactive fluid;

[0087]FIG. 24 shows another container according to an embodiment of theinvention for holding a radioactive fluid;

[0088]FIG. 25 shows another container according to an embodiment of theinvention for holding a radioactive fluid; and

[0089]FIG. 26 shows a flexible plastic shield according to an embodimentof the instant invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0090] According to one aspect of the present invention, an apparatusguided by a guidewire within a patient's artery for reducing restenosisafter arterial intervention in the patient's artery is provided,comprising a radiation dose delivery wire with a radiation sourceencapsulated within its distal end, and a balloon catheter with a blindlumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire, said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0091] The apparatus may further comprise means for providing aliquid-tight seal between the radiation dose delivery wire and theproximal end of the blind lumen.

[0092] The means for providing a liquid-tight seal may comprise aliquid-tight radiation delivery wire port connected to the proximal endof the blind lumen, whereby a liquid-tight seal is effectuated betweenthe proximal end of the blind lumen and the radiation dose deliverywire. Alternatively, the means for providing a liquid-tight seal mayeffectuate a liquid-tight seal between the proximal end of the blindlumen and an afterloader which drives the radiation dose delivery wire.

[0093] The radiation source may be a pellet, a wire, an encapsulatedradiation source, or an attached radiation source, such as a paste ofIr-192, I-125, or Pd-103. Alternatively, the radiation source may be aγ-radiation emitting isotope, such as, for example, one of thefollowing: ¹⁰⁹Cd, ¹¹³Sn, ¹²⁵Te, ¹²⁵I, ⁹³Mo, 133 Ba, ¹⁴⁵Sm, ¹⁴⁷Eu, ⁶Gd,¹⁵⁷Tb, ²⁵⁴Es, 242Am, ¹⁶⁹Yb, ¹⁸⁶Re, ¹⁷³Lu, ¹⁷²Hf, ¹⁷⁷Lu, ¹⁷⁹Hf, ¹⁸³Re,⁴⁴TI, ¹⁷⁸Hf, ⁵⁷Co, ¹⁷⁸Hf, ⁵⁷, ¹⁰¹Rh, ⁷⁵Se, ¹²³Te, ¹³⁹Ce, ¹⁶⁶Ho, ²³⁵U,¹⁰¹Rh, ⁶⁸Tm, ¹⁷⁶Lu, ¹²⁷Xe, ⁹⁵Te, ¹⁷⁷Lu, ¹²¹Te, ²¹⁰Bi, ¹⁸²Hf, ²⁰³Hg,¹⁷⁶Lu, ¹⁹²Ir, ¹⁹⁴Ir, ¹⁵⁰Eu, ¹⁷⁵Hf, ²⁴⁹Cf, ⁸⁸Zr, ⁷⁵Se, ²¹⁰Bi, ¹⁸²Hf,²⁰³Hg, ¹⁷⁶Lu, ¹⁷⁸Hf, ⁹⁵Te, ¹²¹Te, ²⁰³Hg, ¹⁹²Ir, ¹⁷⁸Hf, ¹⁵⁰Eu, ²⁴⁹Cf,⁸⁸Zr.

[0094] The length of the radiation source is determined by the length ofthe segment of diseased vessel, that is, the segment of vessel which isto receive a dose of radiation. The radiation source may be 0.05 to 50cm in length and it may comprise a plurality of radioactive pelletsforming a linear array.

[0095] The apparatus may further comprise means for moving the distalend of said radiation dose delivery wire to a predetermined positionwithin said blind lumen for a predetermined period of time. The meansfor moving may be a computer controlled afterloader. The computercontrolled afterloader may calculate said predetermined position andsaid predetermined time.

[0096] The computer controlled afterloader may further calculate saidpredetermined position and said predetermined time based upon aplurality of input variables including a half-life of the radiationsource, an activity level of the radiation source, an angiograghic orultrasound determined diameter of said artery, and a desired radiationdosage to be delivered to the artery at the predetermined position. Auser may input a plurality of values each representing respective onesof the plurality of input variables to the computer controlledafterloader. The computer controlled afterloader may oscillate saiddistal end of said radiation dose delivery wire back and forth in thearea of the predetermined position for a predetermined period of time.

[0097] An outer diameter of the guidewire and an outer diameter of theradiation dose delivery wire may be substantially equal. The radiationdelivery wire may be less than 2 inches in radius. The radiation sourcemay have a radioactivity of less than about 10 Curies per centimeter ofsource.

[0098] The apparatus may further comprise a radiation blocking shieldmovable between the radiation source within the patient's artery and auser of the apparatus. The radiation blocking shield may be concrete,lead, or plastic.

[0099] According to another aspect of the present invention, anapparatus inserted into a sheath in a patient's artery and guided by aguidewire within the patient's artery for reducing restenosis afterarterial intervention in the patient's artery is provided, comprising aradiation dose delivery wire with a radiation source encapsulated withinits distal end, and a balloon catheter with a blind lumen sealed at itsdistal end and a guidewire lumen extending therethrough to accept saidguidewire, said blind lumen being adapted to accept said radiation dosedelivery wire into its proximal end, said balloon catheter being adaptedto be inserted into said sheath.

[0100] The apparatus may further comprise means for providing aliquid-tight seal between the radiation dose delivery wire and theproximal end of the blind lumen.

[0101] The apparatus may further comprise means for maintaining anextended coaxial relationship between the proximal end of said sheathand the proximal end of said blind lumen.

[0102] According to another aspect of the present invention, anapparatus guided by a guidewire within a patient's artery for reducingrestenosis after arterial intervention in the patient's artery isprovided, comprising a radiation dose delivery wire with a radiationsource encapsulated within its distal end, and a balloon catheter with ablind lumen sealed at its distal end and a guidewire lumen extendingpartially through said balloon catheter, said blind lumen being adaptedto accept said radiation dose delivery wire into its proximal end, saidguidewire lumen having an entry port located at a distal end of saidballoon catheter and an exit port located upon a circumferential surfaceof said balloon catheter.

[0103] According to another aspect of the present invention, anapparatus for reducing restenosis after arterial intervention in apatient's artery is provided, comprising a guidewire for insertion intothe patient's artery at least as far as a target area of the artery, aradiation dose delivery wire with a radiation source encapsulated withinits distal end, and a balloon catheter with a blind lumen sealed at itsdistal end and a guidewire lumen extending therethrough to accept saidguidewire, said blind lumen being adapted to accept said radiationdelivery wire into its proximal end.

[0104] According to another aspect of the present invention, anapparatus guided by a guidewire within a patient's artery for reducingrestenosis after arterial intervention in the patient's artery isprovided, comprising a radiation dose delivery wire with a radiationsource encapsulated within its distal end, and a catheter with a blindlumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire, said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0105] The apparatus may further comprise means for providing aliquid-tight seal between the radiation dose delivery wire and theproximal end of the blind lumen.

[0106] According to another aspect of the present invention, anapparatus to be inserted into a catheter for reducing restenosis afterarterial intervention in a patient's artery is provided, comprising aradiation dose delivery wire with a radiation source encapsulated withinits distal end, and a blind lumen open at its proximal end and sealed atits distal end, said blind lumen being adapted to accept said radiationdose delivery wire into its proximal end and to be inserted into saidcatheter.

[0107] The apparatus may further comprise means for providing aliquid-tight seal between the radiation dose delivery wire and theproximal end of the blind lumen.

[0108] According to another aspect of the present invention, a method ofreducing restenosis after arterial intervention in a patient's artery isprovided, comprising inserting a guidewire into the patient's arteryuntil a distal end of the guidewire is at least as far into the arteryas a predetermined section of the artery, inserting the guidewire into aguidewire lumen of a balloon catheter with a blind lumen, inserting theballoon catheter with the blind lumen into the patient's artery at leastas far as the predetermined section of the artery, inserting a radiationdose delivery wire into said blind lumen in said balloon catheter,moving said radiation dose delivery wire a predetermined distance intothe blind lumen of the balloon catheter for a predetermined period oftime, and removing said radiation dose delivery wire from said blindlumen of said balloon catheter after said predetermined period of time.

[0109] The method of moving said radiation dose delivery wire apredetermined distance into the blind lumen of the balloon catheter fora predetermined period of time may result in the distal end of theradiation dose delivery wire being adjacent said predetermined sectionof artery.

[0110] The method of moving said radiation dose delivery wire apredetermined distance into the blind lumen of the balloon catheter fora predetermined period of time may further comprise determining wherethe predetermined section of artery is, determining a diameter of saidpredetermined section of artery, and determining a desired radiationdosage to be delivered to the predetermined section of artery. Thediameter may be determined by an angiograghic or ultrasound procedure.

[0111] The method of moving said radiation dose delivery wire apredetermined distance into the blind lumen of the balloon catheter fora predetermined period of time may further comprise oscillating saidradiation dose delivery wire back and forth when said distal end ofradiation dose delivery wire is substantially adjacent saidpredetermined section of artery. Alternatively, the radiation dosedelivery wire may be moved from a first position in the blind lumen to asecond position in the blind lumen, with or without stops in between.

[0112] According to another aspect of the instant invention an apparatusfor use with a guidewire for reducing restenosis after arterialintervention in a patient's artery is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's artery,said balloon catheter having a radiation producing coating on aninternal surface.

[0113] The radiation producing coating may include a material selectedfrom the group consisting of Al-26, Sn-123, K-40, Sr-89, Y-91, Ir-192,Cd-115, P-32, Rb-86, I-125, Pd-103, and Sr-90, or any other materialselected from Table 2, for example.

[0114] The radiation producing coating may comprise a lacquer, a glue,an acrylic, or a vinyl.

[0115] The balloon portion of the catheter may be formed of a medicalgrade plastic such as a material selected from the group consisting ofpolyethylene, PET, and nylon.

[0116] According to another aspect of the instant invention an apparatusfor use with a guidewire for reducing restenosis after arterialintervention in a patient's artery is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's artery,said balloon catheter having a radiation producing coating on anexterior surface.

[0117] The radiation producing coating may include a material selectedfrom the group consisting of Al-26, Sn-123, K-40, Sr-89, Y-91, Ir-192,Cd-115, P-32, Rb-86, I-125, Pd-103, and Sr-90, or any other materialselected from Table 2, for example.

[0118] The radiation producing coating may comprise a lacquer, a glue,an acrylic, or a vinyl.

[0119] The balloon portion of the catheter may be formed of a plasticmaterial selected from the group consisting of polyethylene, PET, andnylon.

[0120] According to another aspect of the instant invention an apparatusfor use with a guidewire for reducing restenosis after arterialintervention in a patient's artery is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's artery,said balloon catheter being formed of a flexible material including aradiation producing source.

[0121] The flexible material may be formed of a plastic materialselected from the group consisting of polyethylene, PET, and nylon.

[0122] The plastic material may be doped or copolymerized with saidradiation producing source.

[0123] The radiation producing source may be chemically bonded to saidplastic material by a covalent bond.

[0124] The radiation producing source may be bonded to said plasticmaterial by an ionic bond.

[0125] The radiation producing source may be bonded to said plasticmaterial by a biotin-avidin link.

[0126] The radiation producing source may be bonded to said plasticmaterial by coextrusion.

[0127] According to another aspect of the instant invention a method forreducing restenosis after arterial intervention in a patient's artery isprovided, comprising inserting a balloon catheter with a fluid deliveryport connected thereto into the patient's artery and inserting aradioactive fluid into the balloon catheter through the fluid deliveryport.

[0128] The radioactive fluid may be selected from the group consistingof fluids containing Cu-61, Se-73, Co-55, Sc-44, Sr-75, Kr-77, Ga-68,In-110, Br-76, Ga-66, Ga-72, Sb-122, Na-24, Si-31, Ge-77, Ho-166,Re-188, Bi-212, Y-90, K-42, Ir-192, I-125, Pd-103, Sr-90, andradioactive sodium-chloride, or any other chemical compound formulatedfrom the isotopes given in Table 3, for example.

[0129] The radioactive coatings of the instant invention may be appliedto the balloon portion of the catheter either at the time of manufactureor at the time of use, by the user. Additionally, bonding of theradioactive source to the ballon catheter material may also be performedeither at the time of manufacture or at the time of use, by the user. Ahost of methods for attaching radioactive moieties to plastic surfacesare known. In general, proteins, nucleic acids, and smaller moleculesmay be adsorbed either covalently or by ionic bonding to variousplastics (15-17). Also existing are techniques to radioactively modifyproteins or nucleic acids (18-24). For additional plastic compositionand radioactive source bonding data see (25) and the documents citedtherein.

[0130] According to another aspect of the instant invention an apparatusguided by a guidewire within a patient's artery for receiving aradiation dose delivery wire with a radiation source encapsulated withinits distal end and for reducing restenosis after arterial interventionin the patient's artery is provided, comprising a balloon catheter witha blind lumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire, said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0131] The apparatus may further comprise means for moving the distalend of said radiation dose delivery wire to a predetermined positionwithin said blind lumen for a predetermined period of time.

[0132] The apparatus may further comprise means for providing aliquid-tight seal between the radiation dose delivery wire and theproximal end of the blind lumen.

[0133] The means for providing a liquid-tight seal may comprise aliquid-tight radiation delivery wire port connected to the proximal endof the blind lumen, whereby a liquid-tight seal is effectuated betweenthe proximal end of the blind lumen and the radiation dose deliverywire.

[0134] The means for moving may be a computer controlled afterloader.

[0135] The computer controlled afterloader may calculate saidpredetermined position and said predetermined time.

[0136] The computer controlled afterloader may calculate saidpredetermined position and said predetermined time based upon aplurality of input variables including a half-life of the radiationsource, an activity level of the radiation source, a diameter of saidartery, and a desired radiation dosage to be delivered to the artery atthe predetermined position.

[0137] A user may input a plurality of values each representingrespective ones of the plurality of input variables to the computercontrolled afterloader.

[0138] The computer controlled afterloader may move said distal end ofsaid radiation dose delivery wire back and forth in the area of thepredetermined position for a predetermined period of time.Alternatively, the radiation does delivery wire may be moved from afirst position in the blind lumen to a second position in the blindlumen, with or without stops in between.

[0139] According to another aspect of the present invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; aballoon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending therethrough to accept said guidewire; saidblind lumen being adapted to accept said radiation delivery wire intoits proximal end; and means for moving the distal end of said radiationdose delivery wire to a predetermined position within said blind lumenfor a predetermined period of time.

[0140] According to another aspect of the present invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; aballoon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending therethrough to accept said guidewire; saidblind lumen being adapted to accept said radiation dose delivery wireinto its proximal end; and a radiation blocking shield movable betweenthe radiation source within the patient's luminal structure and a userof the apparatus.

[0141] According to another aspect of the instant invention an apparatusinserted into a sheath in a luminal structure of a patient and guided bya guidewire within the patient's luminal structure for treating adisease process is provided, comprising a radiation dose delivery wirewith a radiation source attached to its distal end; a balloon catheterwith a blind lumen sealed at its distal end and a guidewire lumenextending therethrough to accept said guidewire; said blind lumen beingadapted to accept said radiation dose delivery wire into its proximalend; said balloon catheter being adapted to be inserted into saidsheath; and means for providing a liquid-tight seal between theradiation dose delivery wire and the proximal end of the blind lumen.

[0142] According to another aspect of the instant invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiationdose-delivery wire with a radiation source attached to its distal end;and a balloon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending partially through said balloon catheter; saidblind lumen being adapted to accept said radiation dose delivery wireinto its proximal end; said guidewire lumen having an entry port locatedat a distal end of said balloon catheter and an exit port located upon acircumferential surface of said balloon catheter.

[0143] According to another aspect of the instant invention an apparatusguided by a guidewire within a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; and acatheter with a blind lumen sealed at its distal end and a guidewirelumen extending therethrough to accept said guidewire; said blind lumenbeing adapted to accept said radiation dose delivery wire into itsproximal end.

[0144] According to another aspect of the instant invention an apparatuswith a catheter to be inserted into a luminal structure of a patient fortreating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; and ablind lumen open at its proximal end and sealed at its distal end; saidblind lumen being adapted to accept said radiation dose delivery wireinto its proximal end and to be inserted into said catheter.

[0145] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted in a luminal structure of a patientfor treating a disease process is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's luminalstructure; said balloon catheter having a radiation producing coating onan internal surface.

[0146] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted into a luminal structure of a patientfor treating a disease process is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's luminalstructure; said balloon catheter having a radiation producing coating onan exterior surface.

[0147] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted into a luminal structure of a patientfor treating a disease process is provided, comprising a ballooncatheter with a guidewire lumen extending therethrough adapted to accepta guidewire for guiding the balloon catheter in the patient's luminalstructure; said balloon catheter being formed of a flexible materialincluding a radiation producing source.

[0148] According to another aspect of the instant invention a method fortreating a disease process in a luminal structure of a patient isprovided, comprising inserting a balloon catheter with a fluid deliveryport connected thereto into the patient's artery; inserting aradioactive fluid into the balloon catheter through the fluid deliveryport.

[0149] According to another aspect of the instant invention an apparatusguided by a guidewire within a luminal structure of a patient forreceiving a radiation dose delivery wire with a radiation source on itsdistal end and for treating a disease process is provided, comprising aballoon catheter with a blind lumen sealed at its distal end and aguidewire lumen extending therethrough to accept said guidewire; saidblind lumen being adapted to accept said radiation delivery wire intoits proximal end.

[0150] According to another aspect of the instant invention an apparatusfor use with a guidewire inserted into a luminal structure of a patientfor treating a disease process is provided, comprising a radiation dosedelivery wire with a radiation source attached to its distal end; and aballoon catheter with a blind lumen sealed at its distal end a guidewirelumen extending therethrough adapted to accept a guidewire for guidingthe balloon catheter in the patient's luminal structure; said blindlumen being adapted to accept said radiation dose delivery wire into itsproximal end.

[0151] According to another aspect of the instant invention an apparatusfor use with a sheath and a guidewire inserted into a luminal structureof a patient for treating a disease process is provided, comprising aradiation dose delivery wire with a radiation source attached to itsdistal end; and a balloon catheter with a blind lumen sealed at itsdistal end and a guidewire lumen extending therethrough adapted toaccept a guidewire for guiding the balloon catheter in the patient'sluminal structure; said blind lumen being adapted to accept saidradiation dose delivery wire into its proximal end; said ballooncatheter being adapted to be inserted into a sheath in the patient'sluminal structure surrounding said guidewire.

[0152] According to another aspect of the instant invention an apparatusinserted into a luminal structure of a patient for treating a diseaseprocess is provided, comprising a guidewire for insertion into thepatient's luminal structure at least as far as a target area of theluminal structure; a radiation dose delivery wire with a radiationsource attached to its distal end; and a balloon catheter with a blindlumen sealed at its distal end and a guidewire lumen extendingtherethrough to accept said guidewire; said blind lumen being adapted toaccept said radiation delivery wire into its proximal end.

[0153] According to another aspect of the instant invention a method oftreating a disease process in a patient is provided, comprisinginserting a guidewire into a luminal structure of the patient until adistal end of the guidewire is at least as far into the luminalstructure as a predetermined section of the luminal structure; insertingthe guidewire into a guidewire lumen of a balloon catheter with a blindlumen; inserting the balloon catheter with the blind lumen into thepatient's luminal structure at least as far as the predetermined sectionof the luminal structure; inserting a radiation dose delivery wire intosaid blind lumen in said balloon catheter; moving said radiation dosedelivery wire into said blind lumen in said balloon catheter; movingsaid radiation dose delivery wire a predetermined distance into theblind lumen of the balloon catheter for a predetermined period of time;and removing said radiation dose delivery wire from said blind lumen ofsaid balloon catheter after said predetermined period of time.

[0154] The radioactive fluid may be produced by a radioisotopegenerator.

[0155] According to another aspect of the instant invention a method forreducing restenosis after arterial intervention in a patient's artery isprovided, comprising inserting a balloon catheter with a fluid deliveryport connected thereto into the patient's artery, and inserting aradioactive fluid into the balloon catheter through the fluid deliveryport, said radioactive fluid being selected from the group consisting ofradioisotopes that decay with emission of beta plus or beta minusradiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in % perdecay. The radioisotopes may be non-iodine and non-phosphorus based.

[0156] The radioisotopes that decay with emission of beta plus or betaminus radiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in % perdecay, may be selected from the group consisting of NA-24, SI-31, K-42,SC-43, SC-44, CO-55, MN-56, CU-61, NI-65, GA-66, GA-68, ZN-71, GA-72,AS-72, SE-73, BR-75, AS-76, BR-76, GE-77, KR-77, AS-78, Y-85, KR-87,ZR-87, NB-89, Y-90, NB-90, SR-91, Y-92, Y-93, ZR-97, IN-110, AG-112,AG-113, SB-122, SN-127, TE-129, BA-139, LA-140, LA-141, LA-142, PR-142,PR-145, TB-148, PM-150, EU-152, HO-166, RE-188, RE-190, IR-194, BI-212,and radioactive sodium-chloride.

[0157] The radioisotopes that decay with emission of beta plus or betaminus radiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in % perdecay, may be dissolved in an aqueous fluid.

[0158] The radioisotopes that decay with emission of beta plus or betaminus radiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in % perdecay, may be in gas phase.

[0159] According to another aspect of the instant invention an apparatusfor reducing restenosis after arterial intervention in a patient'sartery is provided, comprising a balloon catheter with a fluid deliveryport connected thereto, and a radioactive fluid inserted into theballoon catheter through the fluid delivery port, said radioactive fluidbeing selected from the group consisting of radioisotopes that decaywith emission of beta plus or beta minus radiation, that have ahalf-life of between approximately 1 and 72 hours, that have an averagedecay energy of approximately 500-2000 keV, and that have radiationintensity of greater than or equal to approximately 50%, said radiationintensity being measured in % per decay. The radioisotopes may benon-iodine and non-phosphorus based.

[0160] The radioisotopes that decay with emission of beta plus or betaminus radiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in t perdecay, may be selected from the group consisting of NA-24, SI-31, K-42,SC-43, SC-44, CO-55, MN-56, CU-61, NI-65, GA-66, GA-68, ZN-71, GA-72,AS-72, SE-73, BR-75, AS-76, BR-76, GE-77, KR-77, AS-78, Y-85, KR-87,ZR-87, NB-89, Y-90, NB-90, SR-91, Y-92, Y-93, ZR-97, IN-111, AG-112,AG-113, SB-122, SN-127, TE-129, BA-139, LA-140, LA-141, LA-142, PR-142,PR-145, TB-148, PM-150, EU-152, HO-166, RE-188, RE-190, IR-194, BI-212,and radioactive sodium-chloride.

[0161] The radioisotopes that decay with emission of beta plus or betaminus radiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in % perdecay, may be dissolved in an aqueous fluid.

[0162] The radioisotopes that decay with emission of beta plus or betaminus radiation, that have a half-life of between approximately 1 and 72hours, that have an average decay energy of approximately 500-2000 keV,and that have radiation intensity of greater than or equal toapproximately 50%, said radiation intensity being measured in % perdecay, may be in gas phase.

[0163] According to another aspect of the instant invention adual-balloon catheter for treating a disease process in a luminalstructure of a patient is provided, comprising an inner balloon, anouter balloon substantially concentric with and substantiallysurrounding the inner balloon, an inner balloon fluid delivery lumen influid connection with the inner balloon, and an outer balloon fluiddelivery lumen in fluid connection with the outer balloon.

[0164] The dual-balloon catheter may further comprise a guidewire lumenconnected to an outer surface of said outer balloon. The inner lumenfluid delivery lumen, the outer lumen fluid delivery lumen, and theguidewire lumen may be in substantially axial alignment.

[0165] The dual-balloon catheter may further comprise a guidewire lumenextending through the outer balloon.

[0166] The inner lumen fluid delivery lumen, the outer lumen fluiddelivery lumen, and the guidewire lumen may be in substantially axialalignment.

[0167] The dual-balloon catheter may further comprise a guidewire lumenextending through the outer lumen and the inner lumen.

[0168] The inner lumen fluid delivery lumen, the outer lumen fluiddelivery lumen, and the guidewire lumen may be in substantially axialalignment.

[0169] The inner balloon may have a radiation producing coating. Theouter balloon may have a radiation producing coating.

[0170] An interior surface of the outer balloon and/or an interior orexterior surface of the inner balloon may be coated with a hydrogel forabsorbing a fluid therein.

[0171] According to another aspect of the instant invention a method fortreating a disease process in a luminal structure of a patient isprovided, comprising inserting into the luminal structure a dual-ballooncatheter including an inner balloon, an outer balloon substantiallyconcentric with and substantially surrounding the inner balloon, aninner balloon fluid delivery lumen in fluid connection with the innerballoon, and an outer balloon fluid delivery lumen in fluid connectionwith the outer balloon, and inserting a radioactive fluid into at leastone of the inner balloon and the outer balloon through the inner balloonfluid delivery lumen and the outer balloon fluid delivery lumen,respectively.

[0172] According to another aspect of the instant invention anindiflator for inserting fluid into a balloon catheter is provided,comprising an elongated tube for holding the fluid, the elongated tubehaving a first end and a second end, the first end of the elongated tubehaving a wall across the tube with a port therein for providing a fluidpassage between an interior of the tube and an exterior of the tube, aplunger assembly including a plunger head with a first face and a secondface and a plunger stem having first and second ends, the plunger headbeing adapted to slide within the tube and being connected to the firstend of the plunger stem, lock means disposed at the second end of thetube for accepting and releasably locking the plunger stem, the secondend of the plunger stem being disposed outside the tube, and a pressurevalve disposed adjacent the second end of the plunger stem and beingoperatively connected to a pressure transducer on the second face of theplunger head facing the first end of the tube, whereby the pressurevalve displays a pressure in an area of the tube between the first endof the tube and the second face of the plunger head.

[0173] The area of the tube between the first end of the tube and thesecond face of the plunger head may be substantially transparent and maybe calibrated to indicate the volume between the first end of the tubeand the second face of the plunger head. The calibration may be betweenabout 1 and 5 cc's and is in increments of about 0.1 cc.

[0174] The following are dosimetric calculations for various isotopesand source geometries in an attempt to identify the most suitable sourcedesigns for such treatments.

[0175] Methods and Materials:

[0176] Analytical calculations are presented for dose distributions anddose rates for Ir-192, I-125, Pd-103, P-32, and Sr-90 as they mightpertain to intracoronary radiations. The effects of source size andpositioning accuracy are studied.

[0177] Results:

[0178] Accurate source placement, dose rates >5 Gray/minute, sharplydefined treatment volume, and radiation safety are all of concern. Dosesof 10-20 Gray are required to a length of 2-3 cm of vessel wall, whichis 2-6 mm in diameter. The dose distribution must be confined to theregion of the angioplasty, with reduced doses to normal vessels andmyocardium. Beta particle or positron particle emitters have radiationsafety advantages, but may not have suitable ranges for treating largediameter vessels. Gamma emitters deliver relatively large doses tosurrounding normal tissues, and to staff. Low energy x-ray emitters suchas I-125 and Pd-103 may represent a good compromise as might injecting aradioactive liquid directly into the angioplasty balloon.

[0179] Conclusions:

[0180] Accurate source centering is found to be the single mostimportant factor for intracoronary irradiations. If this can beaccomplished then a high energy beta particle or positron particleemitter such as Sr-90 would be the ideal source. Otherwise the gammaemitter Ir-192 may prove optimum. A liquid beta particle or positronparticle source such as P-32 has the optimum geometry, but may be unsafefor use with currently available balloon catheters when formulated as abone-seeking phosphate.

[0181] Several groups have presented data demonstrating that 10-20 Grayof acute radiation delivered locally, via the temporary insertion ofhigh activity gamma emitters at the time of angioplasty can inhibitrestenosis in animal models (12,13). It has also been demonstrated thatpermanent radioactive coronary stents may be effective (10). Highlylocalized external beam therapy has been suggested as well (7,11). Mostdata to date have been obtained using animal models, but anecdotalreports suggest that radioactive treatment of human femoral arteriesproduces similar results (2). Preliminary human trials are being plannedat several centers in the U.S. and Europe.

[0182] Preliminary studies have made use of currently availableradioactive sources as none have been specifically designed forintracoronary treatments. Several manufacturers are considering modifiedHigh Dose Rate (HDR) afterloaders for this purpose. It therefore seemsappropriate to identify the most suitable isotope and source design forsuch a device.

[0183] The design criteria are formidable. Doses of 10-20 Gray arerequired to a length of 2-3 cm of the vessel wall, which is 2-6 mm indiameter. The dose distribution should be tightly confined to the regionof the angioplasty, with greatly reduced doses to normal vessels and themyocardia.

[0184] Dose rates on the order of 5 Gray/minute are required in order tomaintain treatment times within tolerable limits. This immediatelysuggests HDR afterloading, perhaps with specially designed sourcessuitable for insertion into standard or modified catheters.

[0185] Current angiographic techniques utilize open ended catheterswhich are flexible enough to be pushed through >100 cm of artery, andable to negotiate multiple bends between the femoral and coronaryarteries. They must also pass through vessels as small as 3 mm diameterwith small radii of curvature. The radioactive source must have similarflexibility. Source integrity is of great importance as dislodgementinto a coronary artery could be fatal.

[0186] Most intraluminal studies to date have used Ir-192 seeds of 10-20mCi activity. Typical seed dimensions are 0.5 mm diameter, 3 mm length(Best Industries, Springfield Va.). Multiple seed arrays are used withspacing 0.5 cm embedded in a 1 mm diameter plastic catheter. While thesesources have proven useful for preliminary studies, the relatively highenergy and low dose rates are not ideal. The need for specialized sourceand catheter design is obvious. For this reason, P-32, Sr-90, and otherbeta particle or positron particle emitters have been suggested.

[0187] Beta particle or positron particle emitters have obviousradiation safety advantages, useful for permitting treatments in theangiographic fluoroscopy suite. As we will show however beta particle orpositron particle ranges may not be suitable for treating largerdiameter vessels. Lower energy gamma and x-ray emitters such as I-125and Pd-103 may represent a good compromise, but are not currentlyavailable at the required specific activities. Other possibilitiesinclude injecting a radioactive liquid directly into the angioplastyballoon.

[0188] We compare five isotopes for potential use in intracoronaryirradiation: Ir-192, I-125, Pd-103, P-32, and Sr-90. While othersuitable isotopes may exist, these five are all commercially available,although not necessarily in the form or activity required forintracoronary irradiation. They also represent the three main categoriesof possible isotopes, namely high energy gamma emitter, low energygamma/x-ray emitter, and beta particle or positron particle emitter. Thebasic properties of each isotope are given in Table 1.

[0189] Ir-192 undergoes beta minus decay, but the therapeutically usefulradiations are the 7 de-excitation gammas of the daughter nucleus Pt-192which range in energy from 296-612 keV with an average energy of 375keV. I-125 and Pd-103 both decay via electron capture with thetherapeutically useful radiations being primarily characteristic x-raysfrom the daughter nuclei, Te-125 and Rh-109, respectively.

[0190] P-32 is a pure beta minus emitter which decays directly to theground state of S-32 with a transition energy of 1.71 MeV. Sr-90 is apure beta minus emitter with a half life of 28 years. It decays to Y-90,also a pure beta particle or positron particle emitter with a half lifeof 64 hours.

[0191] The strontium and yttrium are in radioactive equilibrium, withthe higher energy yttrium beta particle or positron particles (2.27versus 0.54 MeV transition energy) providing most of the therapeuticallyuseful radiation.

[0192] Given these basic isotopic properties, we consider a sourceconsisting of a small metallic seed, similar to those currently used forconventional brachytherapy and HDR. Seeds would have dimensions on theorder of ≦1 mm diameter and 1-3 mm length. Treatment with such a sourcewould require either multiple sources on a line (such as those currentlyavailable for conventional afterloading), or programmable sourceplacement (similar to conventional HDR units) to permit treatment of 2-3cm of vessel wall. The source could in theory be inserted directly intothe coronary artery, or more likely, inserted into a conventional orslightly modified balloon catheter. In either case, as we will showlater, it is highly desirable that the source be centered within thecoronary artery to insure a uniform dose to the arterial walls.

[0193] To optimize source design we need to know the radial dosedistribution, and the dose rate per mCi activity. The axial dosedistribution is of less concern, as this can be optimized by suitablyweighting the source dwell times as in conventional HDR. We assume thatfor each of the isotopes listed in Table 1, a suitable source can befabricated. For comparison purposes only we consider first a singlesource of 0.65 mm diameter and 5 mm length, with the axial positionprogrammable to enable treatment of any length of arterial wall.

[0194] For gamma and x-ray emitters the radial dose distributions frompoint or line sources are well known on theoretical considerations. Manymeasurements have been reported as well, although measurements atdistances less than several millimeters are difficult due to technicalconsiderations. AAPM Task Group-43 (TG-43) (9) has reviewed theavailable data and presented recommendations for calculating dose:

Dose (r,⊖)=S*┌*G(r,⊖)*g(r)*F(r,⊖)  Eq. 1

[0195] where:

[0196] S=air kerma strength

[0197] ┌=dose rate constant

[0198] r=radial distance from source

[0199] ⊖=angle from point of interest to center of source, as measuredfrom the axial dimension of the source (we consider here ⊖=90°

[0200] G=“geometry factor” resulting from spatial distribution of theradioactivity within the source. For a 3 mm long line source, G(r,⊖)∝r⁻²for ⊖90°

[0201] g=radial dose function, given as${\sum\limits_{i}{a_{i}*r^{i}}},$

[0202] where:

[0203] a_(i)=fitted parameters to a fifth order polynomial

[0204] F=anisotropy factor describing dose variation versus angle. Thisfunction is normalized to unity at ⊖=90°

[0205] In practice, for distances <1 cm and ⊖90° all of the correctionfactors in Equation 1 are approximately unity as photon attenuation andphoton scatter very nearly cancel.

[0206] Williamson and Zi (14) have shown that for the Ir-192 sourcescurrently used in HDR units radial errors (for r≦1 cm) are <1%, andanisotropy errors (for 3°≦⊖≦150°) are <10%. Dose versus distance thusapproximates the 1/r² law except for the lowest energy x-ray sources.Specific details on all factors in Equation 1, as well as values for S,┌, a_(i), G, g, and F are found in TG-43 (9).

[0207] For beta minus emitters dose versus radial distance from a pointsource can be calculated more directly using the equation:$\begin{matrix}{{{Dose}\quad (r)} = {\int_{E = 0}^{E\quad \max}{{F(E)}*A*k*{S\left( E^{\prime} \right)}*\rho*\quad {{E}/4}{\prod\quad r^{2}}}}} & {{Eq}.\quad 2}\end{matrix}$

[0208] where:

[0209] r=distance in cm

[0210] F(E)=initial fluence of electrons with energy E

[0211] A=activity in mCi

[0212] k=conversion factor from MeV-mCi/gm to Gy/min

[0213] S(E′)=mean restricted stopping power for electron of energy E′ inMeV/cm

[0214] E′=energy of electron with initial energy E at distance r fromthe source

[0215] ρ=density

[0216] Electron ranges and stopping powers were taken from Berger andSeltzer (1). F(E) spectra for P-32 and Sr-90 (in equilibrium with Y-90)were obtained from the literature (3,5).

[0217] The radial dose distributions given by Equations 1 and 2 wereintegrated over the axial length (L) of the source to properly correctfor the distance “r”, and for Equation 1 the anisotropy factors. Thus ata radial distance “r” from a source of axial length “L”: $\begin{matrix}{{{Dose}\quad (r)} = {\int_{X = {{- L}/2}}^{{+ L}/2}{{Dose}\quad \left( {{{Sqr}.\quad {Root}}\quad \left( {r^{2} + x^{2}} \right)} \right)\quad {x}}}} & {{Eq}.\quad 3}\end{matrix}$

[0218] where:

[0219] Dose (r) is given either by Equation 1 or 2.

[0220] For beta particle or positron particle sources it was assumedthat the radioactive isotope was plated on the exterior surface of theseed, and that electron range was insufficient to pass through the seed.Thus, for each radial position, Equation 2 was integrated only over thesolid angle of the source which is “visible” at a distance “r”. For xand gamma sources internal absorption is implicitly included in thefactor F(r,⊖). Absolute dose rates in water per mCi activity were alsocalculated directly from Equations 1-3.

[0221]FIG. 11 presents relative dose versus radial distance for a sourceof 0.65 mm diameter, and 5 mm length, for each isotope. Doses arenormalized to 1.00 at a distance of 2 mm, the approximate radius of atypical coronary artery.

[0222] Ir-192 and I-125 have nearly identical dose distributions, withboth being very nearly equal to inverse square falloff of dose. Pd-103,because of its lower photon energy has a more rapid dose fall off, asattenuation becomes significant even at small distances.

[0223] The beta particle or positron particle emitters P-32 and Sr-90show even more rapid dose fall off versus distance because of the largenumber of low energy electrons in their respective spectra which haveconcomitant short ranges. P-32, with a maximum energy of 1.7 MeV andmean energy of 0.690 MeV (versus 2.27 and 0.970 MeV for Sr-90/Y-90) hasthe greatest dose fall off.

[0224] Source activities required to achieve a dose rate of 5Gray/minute at a radial distance of 2 mm to a 2 cm length of arterialwall are given in Table 1. This equates to a 4 minute treatment time todeliver 20 Gray, varying with the diameter and axial extension of thetreatment volume. As seen in Table 1, suitable X and gamma sourcesrequire activities ≧1 Ci, whereas beta particle or positron particlesources require only tens of mCi. Due to uncertainties in ┌ factors,source anisotropy, and dose variation at distances <0.5 cm the valuesgiven in Table 1 for required activity should be considered approximate.

[0225] Iridium (Best Industries, Springfield, Va.), Phosphorus(Mallinckrodt, Inc., Technical Product Data. St. Louis, Mo.), andStrontium (New England Nuclear, Boston Mass.) sources of suitable sizeand activity can readily be fabricated, although not all are currentlycommercially available. Iodine and Palladium on the other hand presenttechnical problems in fabrication at this time.

[0226] Although the effect is more dramatic for beta particle orpositron particle sources, FIG. 11 shows that even gamma sources haveextremely rapid dose fall off with radial distance. Dose uniformity isthus critically dependent on centering the source with the artery.

[0227] Dose asymmetry can be calculated from FIG. 11, and in FIG. 12 wedemonstrate the magnitude of this asymmetry resulting from inaccuratecentering of a single 5 mm long source of Sr-90, P-32, or Ir-192.Plotted are the ratios of maximum vessel dose to minimum vessel dose invessels of 3 and 5 mm diameter as a function of centering error. Asseen, centering errors as small as 0.5 mm in a 5 mm diameter vesselresult in dose asymmetries ranging from 2.25 for Ir-192 to 2.62 forP-32. This corresponds to deviations from “prescription dose” of +56%and −31% for Ir-192, and +60% and −30% for P-32. Expectedly, themagnitude of the dose asymmetry increases as source energy decreases.Ir-192 thus yields the smallest dose asymmetries, and P-32 the largest.

[0228] If source position is programmed to treat a longer length ofvessel wall dose asymmetries are slightly reduced because dose fall offversus radial distance is less rapid for a line source as compared to apoint source. Accurate source positioning is still of major importancehowever, as FIG. 13 shows significant asymmetries even for a 3 cm longtreatment volume in a 5 mm diameter vessel.

[0229] For any source the radial dose distribution (and subsequent errorresulting from inaccurate source positioning) can be slightly improvedby increasing the source thickness, but this has obvious limitations interms of source flexibility. FIG. 14 shows that for treatment of a 2 cmlength of vessel increasing the diameter of a P-32 source from 0.65 to1.3 mm results in a marginal improvement in dose distribution. Thus, forall sources a minimum size is optimum.

[0230] The dosimetric asymmetry introduced by errors in sourcepositioning can be eliminated if we consider the possibility of using aliquid beta particle or positron particle emitter such as P-32 sodiumphosphate solution, which could be injected directly into theangioplasty balloon, or even coated onto its inner surface. Balloons arenormally inflated with contrast, but they could, in principle, beinflated with P-32 solution. This would have the distinct advantage ofguaranteeing that the radioactive source is in the correct position, andin direct contact with the vessel walls, thus optimizing doseuniformity.

[0231] A typical balloon is 2-3 cm in length (1), and is inflated to thefull diameter (d) of the vessel. Depending on the degree of arterialocclusion, a 2 cm long balloon inflated to a diameter of 3 mm would havea total volume of approximately 0.14 ml (i.e., volume=Πd²1/4). Theresulting radial dose distribution of the balloon can be calculatedusing a slightly modified formulation of Equations 2 and 3, where theintegration is extended over the radial extent of the source. Theequations describing this have been given in reference (10). Theresulting dose distribution is similar to that of P-32 coated seed orwire, as shown in FIG. 14, which compares doses for 20 mm length wiresand a balloon.

[0232] A dose rate of 5 Gray per minute could be achieved from a balloonfilled with a solution of approximately 50 mCi/ml specific activity. Thecatheter running from the femoral to the coronary artery would also befilled with radioactive solution, but since the diameter of this tube is≦0.4 mm (Medtronic Inc., Deerfield Beach, Fla.), the dose rate to normalvessels around this tube would be less than 20% of the treatment dose,depending on the diameter of the vessels. A 20 Gray treatment wouldresult in less than 4 Gray to normal vessel—well below normal tissuetolerance.

[0233] We are thus left with a choice between high energy gamma or betaparticle or positron particle emitters. The desired criteria for asource are: high dose rate per mCi; high specific activity; long halflife; and treatment distance of at least 3-4 mm.

[0234] No available isotope is ideal. Sr-90 has advantages in terms ofspecific activity, dose rate, radiation safety, and half life; whileIr-192 has an advantage in terms of radial dose distribution. Bothisotopes could be fabricated at the required specific activities usingcurrent technology.

[0235] There is a trade off between the increased radial range ofIr-192, and the safety advantages of Sr-90. Although it is a qualitativeassessment, it appears from FIG. 11 that if the radial treatmentdistance was always ≦1.5 mm, Sr-90 would be the isotope of choice. Forlarger treatment distances, Ir-192 would be better.

[0236] The argument however hinges on one's ability to center theradioactive source in the artery. If ideal centering were possible thenany source would provide radial dose homogeneity and Sr-90 would be theisotope of choice. Current catheter design however dose not guaranteecentering, and the increased range of Iridium could be of advantage.

[0237] Based upon dose distributions, dose rate, specific activity, andcommercial feasibility both Ir-192 and Sr-90 could be suitable sourcesfor intracoronary irradiation. Higher energy beta particle or positronparticle sources would be highly desirable, but these invariably haveextremely short half lives. We have shown here that P-32, with atransition energy of 1.7 MeV is marginally acceptable as a possiblesource, so one can rule out any isotopes with lower transition energies.Isotopes with shorter half lives (14 days for P-32) would also prove tobe impractical.

[0238] On the other end of the beta particle or positron particlespectrum, there are no isotopes with half lives greater than Sr-90 (28years) that also have a greater transition energy (2.27 MeV for Sr-90'sdaughter Y-90). This seems to make Sr-90 the beta isotope of choice,although other possibilities exist, such as Sb-124 with a half life of60 days and average energy of 918 keV. Dose distributions for other betaparticle or positron particle isotopes are similar to those shown inFIG. 11, and development of such sources would not alter our basicconclusions.

[0239] The introduction of P-32 solution directly into the angioplastyballoon is particularly attractive in that it eliminates all problems ofdose inhomogeneity and range. With current technology catheters howeverthere is a 1-2% occurrence of balloon failure. If the balloon and 100 cmlength of catheter were completely filled with P-32 solution, and if theballoon failed, there could then be as much as 15 mCi of P-32 releaseddirectly into the blood. Since P-32 as the phosphate moiety is a boneseeking isotope (occasionally used for the treatment of polycythemiavera), this could result in a skeletal dose >9.5 Gy, and a whole bodydose >1.5 Gy² (8)—both unacceptable risks. Alternatively, other chemicalforms of P-32, more rapidly cleared, would not home to the bone marrowand therefore have an acceptable toxicity profile. Still, the dosimetricadvantages of such a treatment seem to warrant further studies ofcatheter design. Another possible solution to this problem would be toidentify a beta particle or positron particle emitter whose chemicalformulation would be more benign and have shorter biological half lives.Such radioactive solutions may be selected from the group consisting offluids containing Cu-61, Se-73, Co-55, Sc-44, Sr-75, Kr-77, Ga-68,In-110, Br-76, Ga-66, Ga-72, Sb-122, Na-24, Si-31, Ge-77, Ho-166,Re-188, Bi-212, Y-90, K-42, Ir-192, I-125, Pd-103, Sr-90, andradioactive sodium-chloride, or any other chemical compound formulatedfrom the isotopes given in Table 3, for example.

[0240] At current prices, Ir-192, Sr-90, and P-32 sources of therequired activities could all be fabricated for approximately $10³-10⁴,not counting development costs. Sr-90 has by far the longest half life(28 years), with Ir-192 (74 days) and I-125 (60 days) lagging farbehind. Cost may therefore be a significant factor in source selection.

[0241] Presented below are other experimental measurements andanalytical calculations for a ⁹⁰Y-chloride-filled balloon which may besuitable for use in endocardia brachytherapy. Similar calculations canbe performed to determine the requisite concentration of a chelatedradionuclide in solution in a balloon catheter for delivery of a desiredradiation dosage to the tissue of the luminal structure.

[0242] Materials and Methods

[0243] Doses of 15-20 gray are required to a length of 2-3 cm of thearterial wall, which is 2-4 mm in diameter. The dose distribution mustbe confined to the region of the angioplasty with minimal dose to normalvessels and myocardium. Dose rates ç5 gray/min would be optimal in orderto limit treatment times are highly desirable as any source or catheterinserted in the artery restricts blood flow and increases the risk ofmyocardial complication and thrombosis.

[0244] Several high-energy beta-minus emitters, such as ⁹⁰Y and ¹⁸⁶Re,are available in liquid form and appear to be promising as fillingagents for a radioactive balloon. Both isotopes can be obtained fromparent-daughter generators at very high specific activities. They could,therefore, be produced locally and economically. Other isotopes, such as¹⁶⁶Ho, and ⁴²K, produced via neutron or proton activation may also provefeasible(36, 37).

[0245] Calculations

[0246]⁹⁰Y is a pure beta-minus emitter with a half-life of 64 h andtransition energy of 2.27 MeV. It can be produced by neutron activationof ⁸⁹Y, or more commonly, from the decay of ⁹⁰Sr which is also a purebeta emitter with half-life of 28 years and transition energy of 0.54MeV. For the experiments reported here ⁹⁰Y was obtained in the form ofyttrium-chloride solution cluted from a ⁹⁰Sr generator with hydro-cloricacid. Specific concentrations ç80 mCi/ml (2.96×10⁹ Bq/ml) can readily beobtained (Nordion International, Ottawa, Canada). ⁹⁰Sr contamination isless than 20 pCi per curie of yttrium (0.002%).

[0247] Dose (in gray) per decay versus radial distance (in cm) from apoint source can be calculated from first principle (38) using theequation: $\begin{matrix}{{{Dose}\quad (r)} = {\int_{E\quad \min}^{E\quad \max}{{F(E)}*C*{S\left( E^{\prime} \right)}*\quad {{E}/4}{\prod\quad r^{2}}}}} & {{Eq}.\quad 4}\end{matrix}$

[0248] where r=distance(cm), F(E)dE=number of electrons emitted perdecay in the energy interval (E+dE) MeV, C=units conversion factor of1.6 E-10 Gy g/MeV, S(E′)=restricted collision stopping power forelectron of energy E′ (MeV/cm), E′=energy at distance r from the sourceof electron with initial energy E, p=density(g/cm³), E_(min)=minimumenergy of electron with range greater than or equal to r,E_(max)=maximum energy of electron as defined by the beta decaytransition energy.

[0249] Electron ranges and stopping powers based on the continuousslowing down approximation (CSDA) are given by Berger and Seltzer (39)and F(E) spectra are known(40, 41). Dose calculations based on stoppingpower tables derived from the CSDA however may introduce errors due torange straggling and Landau energy loss straggling. A more accuratesolution of Eq. 4 via Monte Carlo calculations for several commonisotopes has been presented in the form of dose kernel functions (whichgive directly the dose per beta decay as a function of radial distance)by Simpkin and Mackie (41).

[0250] The dose rate (Gy/s at a point P(x′,y′,z′) resulting from aradioactive-filled balloon can be determined by numerical integration ofthe dose kernel over the volume of the balloon as given by Eq. 5:

Dose rate (p)=∫k(r′)*(A/V)*dV  Eq. 5

[0251] where k(r)=dose kernel=Gy/decay, r′=cm=[(x′−x)²+(y′−r*sin⊖)²+(z′−r*cos ⊖)²]^(½), A/V=activity per unit volume (Bq/cm³),dV=r*dr*de*dx, and the integration is performed over −L/2 x ½, r_(i) rr₀, and 0 ⊖= 2Π.

[0252] Experimental Data

[0253] Gaf-chromic film is used for dosimetric measurements,particularly for brachy-therapy sources. It is nearly tissue equivalent(TE) with near linear response (i.e. optical density (OD) verses dose),requires no post-irradiation processing, and has a large dynamic range(OD increases from approximately 0.1 to 3.0 for doses between 0 and 200gray).

[0254] A TE phantom was constructed in the form of a 5-cm-diam cylinderand cut in half radially to permit insertion of a slice of GAF-chromicfilm. Both the phantom and the film had central holes 3 mm in diam,drilled axially to permit insertion and inflation of the ballooncatheter. Films exposed in this phantom permit determination of the dosedistribution around the balloon, at the site of the angioplasty.

[0255] A second phantom was made, identical to the first except theaxial hole was 1 mm in diameter instead of 3 mm, to match the diameterof the longer shaft section of catheter which contains tubes forinflating the balloon and also the guide wire. This phantom was used fordetermination of the dose to the formal and iliac arteries.

[0256] Both phantoms were assembled with the GAF-chromic film in place.The dilitation catheter balloon (Mansfield/Boston Scientific, Watertown,Mass.) was 3 mm in diameter by 2 cm in length with a 4 atm nominalinflation pressure (15 atmosphere rated burst pressure). The centralchannel was designed for a 0.46 mm guide wire. The balloon was filledwith 14 mCi/ml (5.18×10⁸ Bq/ml) ⁹⁰Y-chloride solution to a pressure of 4atm, resulting in full inflation of the balloon. A total of 1-mlradioactive solution was required to fill the balloon, catheter shaft,pressure syringe, and lure-lock connectors (i.e., three-way stop c). Thevolume of the balloon itself however is only 0.14 ml, with an additional0.1 ml (approximately) required to fill the catheter shaft, making atotal of 0.24 ml inside the patient. The majority of the radio-activeliquid remains in the Luer-lock connectors.

[0257] Several film exposures were made with irradiation times rangingfrom 5-18 h in order to obtain films in the 0.1-3 OD range. First,isodose distributions in the radial place were measured by placing theballoon inside a hole of 3-mm diameter cut through the film and thephantom. The phantom was also sliced axially enabling a second set ofexposures in which the films were placed adjacent to and parallel to thelong axis of the balloon, thus permitting measurement of the axial dosedistribution. Calibration (i.e. H and D) curves for the film wereobtained by exposing films to doses of 6-200 gray with a calibratedcobalt-60 teletherapy source. Differences in film response between gammarays and electrons have been reported to be less than 3% (42).

[0258] All exposed films were analyzed with a 12-bit He—Ne laser scannerwith spatial resolution of 0.1 mm. Optical densities were converted todose based on the H and D curve and compared to calculations fromEq.(5).

[0259] Results

[0260] The measure H and D curve for ⁶⁰Co was found to be linear up todoses of 200 Gy (corresponding OD of approximately 3.0). Agreementbetween measured and calculated radial doses around the balloon is 6%for distance between 2.5 and 5.0 mm from the center of the catheter(i.e., 1,0-3.5 mm from the surface of the balloon).

[0261] Measurement uncertainties include 2% in source calibration(obtained from the manufacturer), 5% in dilution errors, and 3% in filmcalibration. Uncertainties in calculated doses arise almost entirelyfrom errors in the kernel functions, which are difficult to estimate.The kernel functions of Simpkin and Mackie (41) used here however,differ from those given by Berger (43) by approximately 5% at radialdistances 1.5 mm or ¢5.0 mm. One may therefore take 5% as an approximateuncertainty in the calculated dose values. The 6% agreement between ourmeasured and calculated doses is thus well within the estimateduncertainties.

[0262] Also, the fact that the dose around the shaft of the catheter is10-100 times lower than the dose around the balloon, meaning that in aclinical situation the dose to any vessel other than the area prescribedfor treatment would be negligible.

[0263] Air bubbles occasionally get into the balloon in spite of carefulefforts to aspirate the balloon, and fully fill with liquid. The doseimmediately adjacent to such a bubble is seen to be 30% lower than for afilled balloon. It is easily demonstrable via calculations that on theside of the balloon opposite the air bubble, the dose is within 1%-2% ofa fully filled balloon. Thus even with the presence of a small airbubble, the dose uniformity around a liquid-filled balloon is superiorto a solid wire or seed.

[0264] As seen previously, in the radial plane, dose in the axial planealso shown a 20%-30% decrease in dose near the bubble, with good doseuniformity elsewhere, and rapid dose fall-off at distances beyond theends of the balloon. These data, combined with the radial isodosedistributions demonstrate that a radio nuclide filled balloon yields anextremely uniform dose distribution with rapid dose fall-off beyond thetreatment volume.

[0265] Isotopes with short physical half-lives (on the order of 0.25-20h) can most readily be produced locally from radioactive generators. The⁹⁰Sr-⁹⁰Y is one such possibility, but other such as ⁴²Ar-⁴²K,¹⁴⁴Ce-¹⁴⁴Pr, and ¹⁸⁸W-¹⁸⁸Re, are known. Positron emitters instead ofbeta-minus emitters can also be used because positron emitters have thesame dosimetric characteristics as beta-minus emitters.

[0266] Figure Captions

[0267] 11. Radial dose versus distance for Ir-192, I-125, Pd-103, P-32,and Sr-90. Sources are 0.65 mm diameter and 5.0 mm length. Doses havebeen normalized to 1.0 at a radial treatment distance of 2.0 mm.

[0268] 12. Dose asymmetry (defined as maximum/minimum dose to vesselwall) resulting from inaccurate centering of 5 mm long P-32, Sr-90, orIr-192 sources within arteries of 3 and 5 mm diameter. When the sourceis centered in the artery, the dose asymmetry is 1.0.

[0269] 13. Comparison of dose asymmetry for Sr-90 and Ir-192 sources of5 and 30 mm length in a 5 mm diameter vessel. When the source iscentered in the artery, the dose asymmetry is 1.0.

[0270] 14. Radial dose distribution for P-32 wires of 0.65 and 1.3 mmdiameter, and for a 3 mm diameter P-32 balloon. All sources are 20 mmlength. The dose for a 20 mm length Ir-192 source is shown forcomparison. Doses have been normalized to 1.0 at a radial treatmentdistance of 2.0 mm.

[0271] Referring now to the FIGS., FIG. 2 shows a balloon catheteraccording to a first embodiment of the present invention, which can beused to perform the method according to the present invention. Theapparatus is particularly suited for delivering radioactive doses to thecoronary artery. The preferred embodiment will be described withreference to the coronary artery, but this is by way of example, and notlimitation, as the present invention may also be used to deliverradiation to other luminal structures.

[0272] The apparatus comprises a balloon catheter 5 with a guidewirelumen 6 extending entirely through the balloon catheter 5 and a blindlumen 7 which is closed at the distal end of the balloon catheter 5, forreceiving a radiation dose delivery wire 8. The guidewire lumen 6 issized to fit around a guidewire 9 and to allow the guidewire 9 to slidetherein. The length of guidewire 9 is sufficient to allow it to extendpast a target segment of the artery and it may be, for example, greaterthan about 110 cm for use in the coronary artery. For use in otherarteries, the length of guidewire 9 may also be greater than about 110cm or it may be less.

[0273] The outside diameters of the guidewire 9 and the radiation dosedelivery wire 8 may be about 0.014 inch and in this case the insidediameters of the guidewire lumen 6 and the blind lumen 7 are slightlylarger, to permit movement of the balloon catheter 5 over the guidewire9 and movement of the radiation dose delivery wire 8 through blind lumen7.

[0274] The radiation dose delivery wire entry port 11, at the proximalend of the balloon catheter 5, is adapted to receive the radiation dosedelivery wire 8 and to provide a watertight seal. Thus, the radiationdose delivery wire 8 is isolated from contact with the patient's bodyfluids. The balloon inflation port 13 allows inflation of the balloonsection 5 a at the distal end of the balloon catheter 5 in theconventional manner.

[0275] Referring now to FIG. 3, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, it is seen that the guidewire lumen 6 may be offcenter with regard to the balloon catheter 5, while the blind lumen 7,which is adapted to encircle the radiation dose delivery wire 8, may besubstantially in the center of the balloon catheter 5.

[0276] Referring now to FIG. 4, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, it is seen that the radiation dose delivery wire 8may include non-radioactive sections 8 a and 8 b and radioactive section8 c, which has encapsulated or contained within the distal end ofradiation dose delivery wire 8, a linear array of radioactive sources 8d, 8 e, and 8 f, such as pellets of Ir¹⁹², I¹²⁵, Pd¹⁰³, or otherisotopes selected from Table 4, for example. The length of the lineararray of pellets may be less than or equal to about 2 cm for use in thecoronary artery and less than or equal to about 10 cm for use inperiphery arteries. Alternatively, the radioactive source may becomposed of a non-linear array of such radioactive pellets or it may becomposed of a single radioactive pellet. The radioactivity of each ofthe radioactive sources 8 d, 8 e, and 8 f may be less than or equal to10 Curies per centimeter of source.

[0277] Referring now to FIG. 15, wherein the same reference numerals ofFIG. 4 are applied to the same parts and therefore do not requiredetailed description, it is seen that the radiation dose delivery wire 8may include non-radioactive section 8 a and radioactive section 8 c,which may be attached to or on the distal end of radiation dose deliverywire 8.

[0278] Referring now to FIG. 16, wherein the same reference numerals ofFIG. 4 are applied to the same parts and therefore do not requiredetailed description, it is seen that the radiation dose delivery wire 8may include non-radioactive section 8 a and radioactive section 8 c,which may be in the form of a wire wrapped around on the distal end ofradiation dose delivery wire 8.

[0279] The operation of an apparatus to reduce restenosis after arterialintervention according to the first embodiment of the present inventionis as follows. The guidewire 9 is inserted into the patient's artery.The distal end of the guidewire 9 is inserted at least as far as, andpreferably past the target site, that is, the site that is to receivethe dose of radiation. The guidewire 9 is then inserted into theguidewire lumen 6 and the balloon catheter 5 is moved down the guidewiretowards the distal end until the balloon section 5 a is adjacent thetarget site. In the case of a balloon angioplasty procedure the balloonsection 5 a is then inflated and deflated by balloon inflation/deflationinflation means (not shown) connected to the balloon inflation port 13.Alternatively, if it is desired to deliver a dose of radiation to thetarget area without inflating and deflating the balloon section 5 a,such as following an atherectomy or other arterial intervention, theballoon section 1 a need not be inflated and deflated.

[0280] Finally, the radiation dose delivery wire 8 is inserted into theproximal end of the blind lumen 7 within the balloon catheter 5 throughthe radiation dose delivery wire entry port 11. The radiation dosedelivery wire 8 is inserted towards the distal end of the ballooncatheter 5 until the radioactive sources 8 d, 8 e, and 8 f aresubstantially adjacent the target area. The radioactive sources 8 d, 8e, and 8 f are left in place until a desired dosage of radiation hasbeen delivered to the target area and then the radiation dose deliverywire 8 is removed from the balloon catheter 5. The length of time thatthe radioactive sources 8 d, 8 e, and 8 f are left adjacent the targetarea depends upon the activity of the radioactive sources 8 d, 8 e, and8 e, the diameter of the artery at the target area, and the desireddosage to be delivered. It should be noted that the radiation dosedelivery wire 8 may be oscillated back and forth within the blind lumen7 so that the radioactive sources 8 d, 8 e, and 8 f may be shorter thanthe target area while still being able to deliver radiation to theentire target area. In addition, if the radiation dose delivery wire 8is oscillated back and forth, the time that the radioactive sources 8 d,8 e, and 8 f must be left adjacent the target area in order to deliver adesired dosage of radiation will also depend upon the length of thetarget area.

[0281] Alternatively, the guidewire 9 may be inserted into the artery asabove and a conventional balloon catheter without a blind lumen placedover the guidewire 9 and advanced to the target area to be inflated,deflated, and removed from the artery. After removal from the artery,the balloon catheter 5 of the instant invention, with the blind lumen 7may be placed over the guidewire 9 utilizing the guidewire lumen 6 andinserted adjacent the target area in order to allow the radiation dosedelivery wire 8 to be inserted into the blind lumen 7 to deliver adosage of radiation to the target area as described above. Thisprocedure permits the use of a conventional balloon catheter to performan angioplasty procedure before the balloon catheter 5 of the instantinvention is utilized to deliver a dose of radiation.

[0282] The inventive device and method may also be applied to otherluminal structures in a similar manner.

[0283] Referring now to FIG. 5, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, a balloon catheter according to a secondembodiment of the present invention is shown, which can be used toperform the method according to the present invention. In this FIG., acomputer controlled afterloader 15, similar to a conventionalafterloader such as the one distributed by Nucletron Corp., of Columbia,Md., is connected to the proximal end of the radiation dose deliverywire 8 and is utilized to insert the radiation dose delivery wire 8 intothe blind lumen 7 until the radioactive sources 8 d, 8 e, and 8 f areadjacent the target area and to remove the radiation dose delivery wire8 from the blind lumen 7 after a predetermined dosage of radiation hasbeen delivered to the target area.

[0284] The computer controlled afterloader 15 of the present inventiondiffers from the conventional afterloader in that the computercontrolled afterloader 15 of the present invention allows an operator toinput variables representing the activity of the radioactive sources 8d, 8 e, and 8 f, the date that the radioactive sources 8 d, 8 e, and 8 fare being delivered adjacent the target area (to take into account decayof the radioactive sources 8 d, 8 e, and 8 f), the diameter of theartery at the target area, the length of the target area, and the valueof the desired radioactive dose to be delivered to the target area. Thecomputer controlled afterloader 15 then calculates the time that theradioactive sources 8 d, 8 e, and 8 f must be adjacent the target areato deliver the desired radioactive dosage and then moves the radiationdose delivery wire 8 towards the distal end of the balloon catheter 5until the radioactive sources 8 d, 8 e, and 8 f are adjacent the targetarea, waits the calculated time, and then pulls the radiation dose wire8 back out of the balloon catheter 5.

[0285] In addition, the computer controlled afterloader 15 may oscillatethe radiation dose delivery wire 8 back and forth while the radioactivesources 8 d, 8 e, and 8 f are adjacent the target area. In this case thecomputer controlled afterloader 15 would take into account the length ofthe target area and the rate of oscillation in determining the timenecessary to deliver the desired dosage.

[0286] The computer controlled afterloader 15 may include a programmemory for storing a program to calculate the length of time that theradioactive sources 8 d, 8 e, and 8 f must be adjacent the target areato deliver a desired dosage of radiation, a power supply backup, and adatabase memory for storing the number of times that a particularradioactive source has been used.

[0287] Referring now to FIG. 6, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, a balloon catheter 18 according to a thirdembodiment of the present invention is shown, which can be used toperform the method according to the present invention. A clamp 20 may beutilized to maintain an extended coaxial position between the radiationdose delivery wire entry port 11 connected to the proximal end of theblind lumen 7 and a proximal end of a sheath 19, which surroundscatheter 18 at the area of the incision in the patient's body, duringinsertion of the radiation dose delivery wire 8 into the blind lumen 7.

[0288] Referring now to FIG. 7, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, a balloon catheter 21 according to a fourthembodiment of the present invention is shown, which can be used toperform the method according to the present invention. In this FIG., aguidewire lumen 22 extends for a distance less than the length of theballoon catheter 21. That is, the guidewire lumen 22 has an entry point22 a at the distal end of balloon catheter 21 and exit point 22 b alongthe length of balloon catheter 21, rather than at its proximal end.

[0289] As in the first embodiment, the guidewire 9 is inserted into theartery and the guidewire lumen 22 guides the balloon catheter 21 towardsthe distal end of the guidewire 9. Also, as in the first embodiment, theradiation dose delivery wire 8 rides within the blind lumen 23 of theballoon catheter 21.

[0290] Referring now to FIG. 8, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, an apparatus according to a fifth embodiment ofthe present invention is shown, which can be used to perform the methodaccording to the present invention. In this FIG., a radiation shield 25is movable and is adapted to be moved between a patient (not shown) on asupport 24 and an operator of the apparatus (not shown). The radiationshield 25 may, for example, be moveable by means of rollers 25 a, 25 b,25 c, and 25 d mounted to legs 26 a, 26 b, 26 c, and 26 d.

[0291] In operation the balloon catheter 5, not shown in this FIG. 8, isinserted into a patient (not shown) who is supported by the support 24and the radiation shield 25 is moved between an operator of theapparatus and the radiation source 8 d, 8 e, and 8 f within the blindlumen 7 of the balloon catheter 5. The radiation shield 25 is thusadaptable for different sized patients because it is movable and ittherefore provides protection to the doctor and other staff fromover-exposure to radiation.

[0292] Referring now to FIG. 9, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, an apparatus according to a sixth embodiment ofthe present invention is shown, which can be used to perform the methodaccording to the present invention. In this FIG., a catheter without aballoon 27 includes blind lumen 7 and guidewire lumen 6. This embodimentis utilized in a fashion similar to the first embodiment, except here,the apparatus is used only to deliver radiation, and does not have theballoon function of the first embodiment.

[0293] Referring now to FIG. 10, wherein the same reference numerals ofFIG. 2 are applied to the same parts and therefore do not requiredetailed description, an apparatus according to a seventh embodiment ofthe present invention is shown, which can be used to perform the methodaccording to the present invention. In this FIG., a blind lumen 28,which accepts radiation dose delivery wire 8 into its proximal endthrough radiation dose delivery wire entry port 11, is adapted to beremovably inserted into a catheter (not shown). The catheter may be aballoon type catheter or it may be a catheter without a balloon.

[0294] In operation, the catheter is inserted into a patient in theconventional manner. Blind lumen 28 is then inserted into the catheterand, as in the first embodiment, the radiation dose delivery wire 8 isadvanced into the blind lumen 28, through the radiation dose deliverwire entry port 11, until the distal end of the radiation dose deliverywire 8 is adjacent the segment of artery that is to receive aradioactive dose. Also, as in the first embodiment, the radiation dosedelivery wire 8 is withdrawn after a desired dose of radiation has beendelivered to the artery segment. This embodiment is intended primarily,but not exclusively, for procedures in the peripheral vascular areas.

[0295] Referring now to FIG. 17, this FIG. shows a dual-balloon catheteraccording to an embodiment of the present invention. Guidewire lumen 200may be provided for insertion into a patient (not shown) over aguidewire (not shown). Guidewire lumen 200 may pass through outerballoon 202 as well as inner balloon 204. Inner balloon 204 may besubstantially concentric with outer balloon 202. Outer balloon 200 maybe inflated through outer balloon lumen 206 and inner balloon 204 may beinflated through inner balloon lumen 208. The inner and outer balloonsare preferably independently inflatable and the inner balloon lumen andouter balloon lumen may pass inside the guidewire lumen, as shown, ormay pass outside the guidewire lumen. It must be noted that a guidewirelumen does not have to be used with the inventive dual-balloon catheter.

[0296] The inner and outer balloons may both be inflated with aradioactive fluid or either one of them may be so inflated. For thepurposes of this application the term fluid includes an aqueous solutionas well as a gas phase. If only the inner balloon is inflated with aradioactive fluid the outer balloon provides extra protection to thepatient in the case of rupture of the inner balloon (the outer balloonwill help to contain the fluid). If only the outer balloon is inflatedwith the radioactive fluid then a reduced amount of radioactive fluid isrequired to achieve a given radiation therapy.

[0297] In this regard it is noted that the present invention providesfor the reduction in volume of radioactive fluid, minimizes the risk ofrupture, adds shielding, removes the operator from the vicinity of theradioactive fluid, and reduces the reduces the risk of a spill of theradioactive fluid.

[0298] Referring now to FIG. 18, a novel indiflator 220 is shown. Inthis indiflator a plunger head 222 is attached to a plunger stem 224.The plunger stem is threaded and may be locked by lock 226. The plungerstem may be moved in the direction of arrow A in order to force fluidout through port 228, which may be connected to a Luer lock (not shown)and ultimately to a balloon catheter (not shown). A pressure indicator230 measures the pressure of the fluid acted upon by the plunger througha transducer means connected thereto by a connector running in or alongthe stem 224. This arrangement allows for the measurement of pressure asdescribed above while minimizing the volume of fluid acted upon by theplunger. Calibration scale 232 may be provided for measuring fluidvolume and this calibration scale 232 may read from 1 to 5 cc's in 0.1cc increments, for example.

[0299] Referring now to FIG. 19, a shield 240 is shown. This shield mayslid over the indiflator 220 of FIG. 18 and may be provided with aLucite section 242 and a lead section 244 for protecting an operatorfrom the radioactive fluid. The lead section may have a window therein(not shown) to allow an operator to seen the indiflator 220. The Lucitesection 242 may be aligned with the calibration scale 232 of theindiflator 220, for example.

[0300] Referring now to FIG. 20, this FIG. shows a lumen 250 that may beplaced between an indiflator (not shown) or a Luer lock (not shown) anda balloon catheter (not shown). End 252 of the lumen 250 may be attachedto the indiflator or Luer lock, threaded attachment ring 254 may beattached to the balloon catheter and section 255 may be placed withinthe lumen of the balloon catheter to take up space and decrease thevolume of radioactive fluid inserted into the balloon catheter when itis inflated with a fluid, such as a radioactive fluid.

[0301] Referring now to FIG. 21, a 3-way stopcock 260 is shown forconnection between a indiflator (not shown) or a Luer lock (not shown)and a balloon catheter (not shown). Port 262 may be connected to theindiflator or the Luer lock and port 264 may be connected to the ballooncatheter. Port 266 may be used to vent the balloon catheter to theoutside atmosphere or to a syringe (not shown) or storage container (notshown). Handle 268, which controls a valve (not shown) within the 3-waystopcock is moveable along arrow A to allow passage of fluid between twoof the ports. The handle 268 is long in relation to the 3-way stopcockso that an operator's hands are not near the radioactive fluid.

[0302] Referring now to FIG. 22, a case 270 for a 3-way stopcock isshown. The case may include a handle 272 for actuating the 3-waystopcock. The case may also include apertures 274, 276, and 278 forpermitting fluid flow to and from the 3-way stopcock. The case 270 maybe designed to accept a separate 3-way stopcock or may include a 3-waystopcock integrally therewith. The case 270 may be made of, or include alayer of either or both Lucite and lead, for example (to reduce anoperator's exposure to radiation).

[0303] Referring now to FIG. 23, a container 280 for holding aradioactive substance, such as a fluid is shown. A bottom 282 mayunscrew from the top 281 in order to place a bottle with a radioactivefluid inside. A hole 284 in the top may be provided for providing accessto the radioactive fluid inside the container. The hole 284 may becovered with a sealing structure, such as a rubber membrane, forexample, as may be the bottle. This sealing structure may beself-sealing. If a sealing stricture is used, a needle may be employedto pierce the sealing structure and access the radioactive fluid. Theexterior of the container 280 may be lead and the interior may beLucite, for example. Alternatively, the interior may be lead and theexterior Lucite. This two-layer structure provides protection from theradioactive substance contained therein.

[0304] Referring now to FIG. 24, another container 290 for holding aradioactive substance, such as a fluid is shown. A first port 292 may beprovided for inserting a radioactive fluid and a second port 294 may beprovided for removing the radioactive fluid. Like the container 280 ofFIG. 23, the ports may be covered with a sealing structure, such as arubber membrane, for example. This sealing structure may beself-sealing. If a sealing stricture is used, a needle may be employedto pierce the sealing structure and access the radioactive fluid. Theexterior of the container 290 may be lead and the interior may beLucite, for example. Alternatively, the interior may be lead and theexterior Lucite. This two-layer structure provides protection from theradioactive substance contained therein.

[0305] Referring now to FIG. 25, another container 300 for holding aradioactive substance, such as a fluid is shown. A port 302 may beprovided for inserting and removing a radioactive fluid. Like thecontainer 280 of FIG. 23, the port may be covered with a sealingstructure, such as a rubber membrane, for example. This sealingstructure may be self-sealing. If a sealing stricture is used, a needlemay be employed to pierce the sealing structure and access theradioactive fluid. The exterior of the container 300 may be lead and theinterior may be Lucite, for example. Alternatively, the interior may belead and the exterior Lucite. This two-layer structure providesprotection from the radioactive substance contained therein. The topsection 304 may be generally cylindrical and the bottom section 306 maybe conical, or funnel-shaped. The funnel-shaped bottom section 306concentrates the fluid at the bottom of the container 300 in a smallvolume so that it may be removed by a needle placed down into the bottomsection. A mesh 308 with a central hole 308 a may be employed to strainthe fluid and keep relatively large debris above the mesh.

[0306] Referring now to FIG. 25, a flexible plastic shield 310 is shown.This shield 310 may include sections 312 and 314 and may includefasteners 316 such as snaps or Velcro for holding the shield around acontainer or structure with a radioactive source whereby the shieldprotects a person from the radiation given off by the radioactivesource. A flexible plastic shield having a density approximately equalto that of water should be approximately 2 mm thick to contain betaenergy, for example.

[0307] It must be noted that although the present invention is describedby reference to particular embodiments thereof, many changes andmodifications of the invention may become apparent to those skilled inthe art without departing from the spirit and scope of the invention asset forth in the claims. For example, isotopes chosen from the attachedTables may be substituted for those identified elsewhere in theapplication. Further, isotopes that decay to those listed in theapplication may be used. TABLE 1 Basic Properties of Isotopes maximumaverage gamma isotope decay emission energy energy t1/2 factor¹activity² Ir-192 beta- gamma  612 keV 375 keV 74 d 4.6 1000 mCi I-125 ECx-ray   35 keV  28 keV 60 d 1.2 3700 mCi Pd-103 EC x-ray   21 keV  21keV 17 d 1.1 3700 mCi P-32 beta- beta- 1.71 MeV 690 keV 14 d —  36 mCiSr-90 beta- beta- 2.27 MeV 970 keV³ 28 yr —  30 mCi

[0308] average Radiation Radiation Decay Rad. Energy Intensity A ELEMENTMode Half-Life Type (keV) (%) 26 AL EC 7.4E + 5 Y 3 B+ 543.49 7 81.77 17 0.947 123 SN B− 129.2 D 4 B− TOT 522.7 14 100.00 13 1.11 123 SN B−129.2 0 4 B− 525.5 13 99.37 11 1.11 40 X B− 1.277E + 9 Y B− 560.64 1889.27 13 1.07 89 SR B− 50.53 D 7 B− 583.3 13 99.99039 8 1.34 91 Y B−58.51 D 6 B− TOT 603.4 9 100.00 7 1.29 91 Y B− 58.51 D 6 B− 604.9 999.70 5 1.28 115 CD B− 44.4 D 3 B− TOT 605.2 10 99.98 1.29 115 CD B−44.6 D 3 B− 618.3 9 97.00 1.07 89 SR B− 50.53 D 7 B− 583.3 13 99.99039 81.24 91 Y B− 58.51 D 6 B− TOT 603.4 9 100.00 7 1.29 91 V B− 56.51 D 6 B−404.9 9 99.70 5 1.28 115 CD B− 44.6 D 3 B− TOT 605.2 10 99.98 1.29 115CD B− 44.6 D 3 B− 618.3 9 97.00 1.28 86 RB B− 18.631 D 1 B− TOT 668.1 10100.00 6 1.42 32 P B− 14.26 D 4 B− 494.9 3 100.0 1.48 86 RB B− 18.431 D1 B− 709.3 9 91.36 4 1.38

[0309] Radiation Radiation Decay Rad. Energy Intensity A ELEMENT ModeHalf-Life Type (keV) (%) 43 SC EC 3.891 H 12 B+ 508.1 9 70.9 6 0.767 61CU EC 3.333 H 5 B+ 524.2 5 51. 5 0.569 73 SE EC 7.15 M 8 B− 562. 5 65.07 0.778 73 SE EC 7.1.5 H 8 B+ TOT 564. 5 65.7 7 0.769 55 CO EC 17.53 H 3B+ TOT 567.07 21 76. 4 0.917 44 SC SC 3.927 H 8 B+ 632.6 9 94.34 4 1.2790 NB EC 14.60 H 5 B+ 662.2 18 52.1 18 0.721 75 BR EC 96.7 M 13 B+ TOT710. 10 72. 6 1.09 75 BR EC 96.7 M 13 B+ 749. 10 52. 4 0.721 75 BR EC96.7 M 13 B+ TOT 710. 10 72. 6 1.09 75 BR EC 96.7 M 13 B+ 749. 10 52. 40.830 85 Y EC 2.68 H 5 B+ TOT 749. 6 84. 19 1.35 77 KR EC 74.4 M 6 B+760. 14 80. 4 1.30 68 CA EC 67.629 M 2 B+ TOT 829.9 6 89.1 5 1.58 68 GAEC 67.629 M 2 B+ 836.0 4 88.0 4 1.57 39 NB EC 1.18 H 2 B+ 986. 21 65. 61.36 85 Y EC 4.86 H 13 B+ TOT 987. 5 58. 5 1.22 89 NB EC 1.18 H 2 B+986. 21 65. 6 1.36 85 Y EC 4.86 H 13 B+ TOT 987. 5 58. 5 1.22 89 NB EC1.18 M 2 B+ TOT 1002. 22 81. 10 1.73 85 Y EC 4.86 M 13 B+ 1008. 5 52. 41.12 87 ZR EC 1.68 H 1 B− TOT 1009. 5 64.0 6 1.11 110 IM EC 69.1 M 5 B+TOT 1010. 14 62. 4 1.33 87 ZR EC 1.68 H 1 B+ 1012. 5 83.5 6 1.50 110 IMEC 69.1 M 5 B+ 1015. 14 61. 4 1.32 72 AS EC 26.0 H 1 B+ 1117.0 19 64.215 1.10 110 IM EC 69.1 M 5 B+ 1015. 14 61. 4 1.32 72 AS EC 26.0 H 1 B+1117.0 19 64.2 15 1.53 72 AS EC 26.0 H 1 B+ TOT 1167.8 20 87.8 23 2.1876 BR EC 16.2 H 2 B+ TOT 1180. 11 55. 3 1.38 89 NB EC 1.9 H 2 B+ TOT1447. 10 75. 15 2.32 89 NB EC 1.9 H 2 B+ 1462. 9 74. 15 2.30 148 TB EC60 M 1 B+ TOT 3556. 20 51.38 1.71 120 I EC 81.0 M 6 B+ TOT 1657. 9975.34 2.76 148 TB EC 60 M 1 B+ TOT 1558. 20 51.38 1.71 120 I EC 81.0 M 6B+ TOT 1657. 99 78.34 2.75 66 GA EC 9.49 H 7 B+ TOT 1736.4 20 56.1 152.07 72 GA B− 14.10 H 1 B− TOT 501.6 15 100.2 12 1.07 127 SN B− 2.10 H 4B− TOT 511. 74 103. 10 1.12 129 TE B− 69.6 N 2 B− TOT 520.2 19 99. 121.10 122 SB B− 2.7238 D 2 B− 521.2 10 66.73 20 0.741 140 LA B− 1.6781 D7 B− TOT 524.5 10 97.3 25 1.09 71 ZN B− 3.96 H 5 B− 540. 6 99. 3 7.41140 LA B− 1.6781 D 7 B− TOT 534.5 10 97.3 25 1.09 71 ZN B− 3.96 M 5 B−TOT 540. 6 99. 3 1.14 129 TE B− 69.6 M 2 B− 544.5 18 88. 12 1.02 24 NAB− 14.9590 H B− 554.1 3 99.944 4 1.18 71 ZN B− 3.96 H 5 B− 573. 5 69. 31.0 122 SB B−- 2.7238 D 2 B− TOT 574.4 11 97.4 6 1.15 31 SI B− 157.3 M 3B− 595.0 4 99.93 1.27 190 RE B− 3.2 H 2 B− TOT 621 95 53 5 0.703 31 SIB− 157.3 M 3 B− 595.6 4 99.93 1.27 190 RE B− 3.2 H 2 B− TOT 621. 95 53.5 0.703 65 NI B− 2.51719 H B− TOT 627.7 8 100.0 4 1.34 77 GE B− 11.30 H1 B− TOT 641.8 13 100.1 21 1.37 91 SR B− 9.63 H 5 B− TOT 646.6 23 99. 61.37 166 HO B− 26.80 H 2 B− TOT 665.1 6 100. 3 1.42 145 PR B− 5.984 H 10B− TOT 675. 3 97.3 21 1.40 152 EU B− 9.274 H 9 B− TOT 676.9 9 73. 4 1.05145 PR B− 5.984 H 10 B− 683. 3 95.0 20 1.40 152 EU B− 9.274 H 9 B− TOT676.9 9 73. 4 1.05 145 PR B− 5.984 H 10 B− 683. 3 95.0 20 1.38 166 HO B−26.50 H 2 B− 693.6 5 50.0 21 0.739 152 EU B− 9.274 H 9 B− 705.4 8 68. 41.02 97 ZR B− 16.91 H 5 B− TOT 706.6 10 99.4 6 1.50 150 PM B− 2.68 H 2B− TOT 725. 36 100. 6 1.55 97 ZR B− 16.91 H 5 B− 757.0 9 87.8 3 1.42 113AG B− 9.37 H 5 B− TOT 757. 10 100.4 1.62 97 ZR B− 16.91 H 5 B− 757.0 987.8 3 1.42 113 AG B− 5.37 H 5 B− TOT 757. 10 100.4 1.62 188 RE B− 16.98H 2 B− TOT 763.81 19 100.0 21 1.63 212 BI B− 60.55 M 6 B− TOT 769.6 1964.06 14 1.05 113 AG B− 5.37 M 5 B− 791. 10 85.00 1.43 188 RE B− 16.98 H2 B− 735.30 16 70.6 15 1.20 194 IR B− 19.15 H 3 B− TOT 806.8 9 100.0 251.72 142 PR B− 19.12 H 5 B− TOT 809.1 12 100.0 7 1.72 56 MN B− 2.5785 H6 B− TOT 323.9 7 100.1 14 1.72 142 PR B− 19.12 H 5 B− TOT 809.1 12 100.07 1.72 56 MN B− 2.5785 H 6 B− TOT 323.9 7 100.3 14 1.77 212 BI B− 60.55H 6 B− 832.5 17 55.46 10 0.963 142 PR B− 19.12 H 5 B− 833.4 11 96.3 51.71 194 IR B− 19.15 M 3 B− 846.48 8 85.4 20 1.54 142 LA B− 91.1 M 5 B−TOT 872. 4 99.4 10 1.65 65 NI B− 2.51719 M 5 B− 875.4 6 60.0 3 1.13 139BA B− 83.06 M 28 B− TOT 889.6 19 100.0 5 1.69 65 NI B− 2.51719 H B−875.4 6 60.0 3 1.12 139 BA B− 83.06 M 28 B− TOT 889.6 19 100.0 5 1.89139 BA B− 83.06 M 28 B− 913.9 19 70.0 4 1.36 90 Y B− 64.10 H 8 B− 933.712 99.9885 14 141 LA B− 3.92 H 3 B− TOT 962. 12 100.02 22 2.05 141 LA B−3.92 M 3 B− 974. 12 98.14 7 2.04 76 AS B− 1.0778 D 2 B− TOT 1070.0 11100. 3 2.27 93 Y B− 10.18 M 8 B− TOT 1167. 7 100.0 16 2.49 93 Y B− 10.18H 8 B− 1211. 6 89.6 2.5 2.27 93 Y B− 10.18 M 8 B− TOT 1167. 7 100.0 182.49 93 Y B− 10.18 H 8 B− 1211. 6 89.6 15 2.31 56 MN B− 2.5765 H 6 B−1216.9 5 56.3 10 1.46 78 AS B− 90.7 M 2 B− TOT 1244. 7 101. 9 2068 76 ASB− 1.0776 D 2 B− 1266.9 9 51.0 20 1.36 87 KR B− 76.3 M 6 B− TOT 1333. 3100. 4 2.83 112 AG B− 3.130 H 9 B− TOT 1354. 17 105. 6 3.02 42 K B−12.360 H 3 B− TOT 1430.4 7 100.00 13 3.05 92 Y B− 3.54 H 1 B− TOT 1436.6 100.1 21 3.06 92 V B− 3.54 H 1 B− 1553. 5 85.7 16 2.83 42 K B− 12.360H 3 B− 1565.8 6 81.90 9 2.73 112 AG B− 3.130 M 9 B− 1688 14 54 5 1.94

[0310] Radiation Radiation Decay Rad. Energy Intensity A ELEMENT ModeHalf-Life Type (keV) (%) 125 TE IT 57.40 D 15 G X KA1 27.47230 20 61.323 0.0359 125 I EC 59.402 D 1 G X KA1 27.47230 20 74.3 17 0.0435 93 MOEC 3.5E + 3 Y 7 G 30.770 20 82. 5 0.0537 133 BA EC 10.52 Y 13 G X KA130.9728 3 64.9 12 0.0428 145 SM EC 340 D 3 G X KA1 38.7247 5 71.6 120.0591 147 EU EC 24 D 1 G X KA1 40.1181 3 52. 3 0.0447 146 GD EC 48.27 D10 G X KA2 40.9019 3 52.2 8 0.0455 146 GD EC 48.27 D 10 G X KA1 41.54223 94.5 14 0.0836 157 TB EC 99 Y 10 G X KA2 42.3089 3 71. 6 0.0455 146 GDEC 48.27 D 10 G X KA1 41.5422 3 94.5 14 0.0836 157 TB EC 99 Y 10 G X KA242.3059 3 71. 6 0.646 254 ES A 275.5 D 5 G 42.60 10 100.0 0.0907 157 TBEC 99 Y 10 G X KA1 42.9962 3 129. 10 0.118 242 AM IT 141 Y 2 G 48.63 599.50 20 0.103 157 TB EC 99 Y 10 G X KS 48.70 51. 4 0.0528 169 YB DC32.026 D 5 G X KA2 49.7726 4 53.0 10 0.0562 186 RE IT 2.0E + 5 Y 5 G 50.37 88. 3 0.0936 169 YB EC 32.026 D 5 G X KA2 49.7726 4 53.0 10 0.0562186 RE IT 2.0E + 5 Y 5 G 50. 37 88. 3 0.0936 169 YB EC 32.026 D 5 G XKA1 50.7416 4 93.5 18 0.101 173 LU EC 1.37 Y 1 G X KA1 52.3889 5 77.2 210.0862 172 HF EC 1.87 Y 3 C X KA1 54.0698 5 64. 7 0.0734 177 LU B− 160.4D 3 G X KA1 55.7902 8 58.0 11 0.0490 179 HF IT 25.05 D 25 G X KA155.7902 8 56.4 19 0.0670 183 RE EC 70.0 D 11 G X KA1 59.31820 10 59.9 200.0757 44 TI EC 49 Y 3 G 67.39 94.4 15 0.0862 172 HF EC 1.87 Y 3 C X KA154.0698 5 64. 7 0.0734 177 LU B− 160.4 D 3 G X KA1 55.7902 8 58.0 110.0690 179 HF IT 25.05 D 25 G X KA1 55.7902 8 56.4 19 0.0670 183 RE EC70.0 D 11 G X KA1 59.31820 10 59.9 20 0.0751 44 TI EC 49 Y 3 G 67.8894.4 15 0.136 243 AM A 7370 Y 15 G 74.660 20 68.2 14 0.108 44 TI EC 49 Y3 G 71.34 96.2 3 0.161 178 HF IT 31 Y 1 G 88.862 6 64.4 14 0.122

REFERENCES

[0311] 1. Berger, M. J. and Seltzer, S. M. Stopping powers and ranges ofelectrons and positrons (2nd Ed.). U.S. Dept. Commerce Publication NBSIR82-2550-A (1983)

[0312] 2. Bottcher, H. D., Schopohl, B., Liermann, D., Kollath, J., andAdamietz, I. A. Endovascular irradiation-a new method to avoid recurrentstenosis after stent implantation in peripheral arteries: technique andpreliminary results. Int. J. Rad. Onc. Biol. Phys. 29, 183-186 (1994)

[0313] 3. Friedell, H. L., Thomas, C.I., and Krohmer, J. S. Descriptionof an Sr⁹⁰ beta-ray applicator and its use on the eye. Amer. J. Roentg.65, 232-245 (1951)

[0314] 4. Gellman, J., Healey G., Qingsheng, C., Tselentakis, M. J. Theeffects of very low dose irradiation on restenosis following balloonangioplasty. A study in the atherosclerotic rabbit. Circulation 84,Supple 11, 46A-59A (1991)

[0315] 5. Johns, H. E., and Cunningham, J. R. The Physics of Radiology(4th Edition). Charles Thomas, Publisher (Springfield, Ill., 1983).

[0316] 6. Landau, C., Lange, R. A., Hillis, L. D. Percutaneoustransluminal coronary angioplasty. NEJM 330, 981-993 (1994)

[0317] 7. Mayberg, M. R., Luo, Z., London, S., Gajdusek, C., Rasey, J.S. Radiation inhibition of intimal hyperplasia after arterial injury.Rad. Res. 142, 212-220 (1995)

[0318] 8. MIRD. Method of calculation: “S”, absorbed dose per unitcumulated activity for selected radionuclides and organs. MIRD Pamphlet#11 (1975).

[0319] 9. Nath, R., Anderson, L., Luxton, G., et. al. Dosimetry ofinterstitial brachytherapy sources: recommendations of the AAPMradiation therapy committee task group No. 43. Med. Phys. 22, 209-234(1995)

[0320] 10. Prestwich, W. V., Kennet, T. J., and Kus, F. W. The dosedistribution produced by a P³²-coated stent. Med. Phys. 22, 313-320(1995)

[0321] 11. Schwartz, R. S., Koval, T. M., Edwards, W. D., Camrud, A. R.,Bailey, K. R., Brown, K., Vlietstra, R. E., and Holmes, D. R. Effect ofexternal beam irradiation on neointimal hyperplasia after experimentalcoronary artery injury. J. Am. Col. Cardiol. 19, 1106-1113 (1992).

[0322] 12. Wiederman, J., Marobe, C., Amols, H., Schwartz, A., andWeinberger, J. Intracoronary irradiation markedly reduces restenosisafter balloon angioplasty in a porcine model. J. Amer. Col. Card. 23,1491-8 (1994)

[0323] 13. Wiederman, J., Leavy, J., Amols, H., Schwartz, A., Homma, S.,Marobe, C., and Weinberger, J. Effects of high dose intracoronaryirradiation on vasomotor function and smooth muscle histopathology. Am.J. Phys. (Heart and Circ. Physiol.) 267, H125-H132 (1994)

[0324] 14. Williamson, J. F., and Zuofend, L. Monte carlo aideddosimetry of the microselectron pulsed and high dose-rate ¹⁹²Ir sources.Med. Phys. 22, 809-819 (1995)

[0325] 15. Desai, N. P., & Hubbell, J. A. (1991). Biological responsesto polyethylene oxide modified polyethylene terephthalate surfaces.Journal of Biomedical Materials Research, 25(7), 829-43.

[0326] 16. Gombotz, W. R., Wang, G. H., Horbett, T. A., & Hoffman, A. S.(1991). Protein adsorption to poly (ethylene oxide) surfaces. Journal ofBiomedical Materials Research, 25(12), 1547-62.

[0327] 17. Massia, S. P., & Hubbell, J. A. (1991). Human endothelialcell interactions with surface-coupled adhesion peptides on anonadhesive glass substrate and two polymeric biomaterials. Journal ofBiomedical Materials Research, 25(2), 223-42.

[0328] 18. Afshan, A., Jehangir, M., Ashraf, M., Waqar, A., &Chiotellis, E. (1994). Formulation of a single-component kit for thepreparation of technetium-99m labeled ethyl cysteinate dimer; biologicaland clinical evaluation. European Journal of Nuclear Medicine, 21(9),991-5.

[0329] 19. Hannant, D., Bowen, J. G., Price, M. R., & Baldwin, R. W.(1980). Radioiodination of rat hepatoma-specific antigens and retentionof serological reactivity. British Journal of Cancer, 41(5), 716-23.

[0330] 20. Hartikka, M., Vihko, P., Sodervall, M., Hakalahti, L.,Torniainen, P., & Vihko, R. (1989). Radio labeling of monoclonalantibodies: optimization of conjugation of DTPA to F(ab′)2-fragments anda novel measurement of the degree of conjugation using Eu(III)-labeling.European Journal of Nuclear Medicine, 15(3), 157-61.

[0331] 21. Ingvar, M., Eriksson, L., Rogers, G. A., Stone, E. S., &Widen, L. (1991). Rapid feasibility studies of tracers for positronemission tomography: high-resolution PET in small animals with kineticanalysis. Journal of Cerebral Blood Flow & Metabolism, 11(6), 926-31.

[0332] 22. Portoles, P., Rojo, J. M., & Janeway, C. J. (1990). A simplemethod for the radioactive iodination of CD4 molecules. Journal ofImmunological Methods, 129(1), 105-9.

[0333] 23. Samuel, D., Amlot, P. L., & Abuknesha, R. A. (1985). A newmethod of iodinating ovalbumin, a protein which lacks accessibletyrosine groups, by conjugation to a highly fluorescent coumarin activeester, CASE. Journal of Immunological Methods, 81(1), 123-30.

[0334] 24. Wafelman, A. R., Konings, M. C., Hoefnagel, C. A., Maes, R.A., & Beijnen, J. H. (1994). Synthesis, radiolabelling and stability ofradioiodinated m-iodobenzylguanidine, a review. [Review]. AppliedRadiation & Isotopes, 45(10), 997-107.

[0335] 25. Polymers FAQ, Polymers archive on the Internet complied byJim Coffey, Aug. 11, 1995.

[0336] 26. Abayomi, O., Chun, M., & Ball, H. (1990). Stage II carcinomaof the cervix: analysis of the value of pretreatment extraperitoneallymph node sampling and adjunctive surgery following irradiation.Radiotherapy & Oncology, 19(1), 43-7.

[0337] 27. Ampil, F. L. (1985). Primary malignant neoplasm of the femaleurethra. Obstetrics & Gynecology, 66(6), 799-804.

[0338] 28. Beauvois, S., Hoffstetter, S., Peiffert, D., Luporsi, E.,Carolus, J. M., Dartois, D., & Pernot, M. (1994). Brachytherapy forlower lip epidermoid cancer: tumoral and treatment factors influencingrecurrences and complications. Radiotherapy & Oncology, 33(3), 195-203.

[0339] 29. Broga, D. W., & Gilbert, M. A. (1983). A review of threeincidents involving the release of 125I from seeds interstitiallyimplanted within the prostate gland. Health Physics, 45(3), 593-7.

[0340] 30. Cotter, G. W., Lariscy, C., Ellingwood, K. E., & Herber, D.(1993). Inoperable endobronchial obstructing lung cancer treated withcombined endobronchial and external beam irradiation: a dosimetricanalysis. International Journal of Radiation Oncology, Biology, Physics,27(3), 581-5.

[0341] 31. George, F. (1980). Radiation management in esophageal cancer.With a review of intraesophageal radioactive iridium treatment in 24patients. American Journal of Surgery, 139(6), 795-804.

[0342] 32. Layery, I. C., Jones, I. T., Weakley, F. L., Saxton, J. P.,Fazio, V. W., & Jagelman, D. G. (1987). Definitive management of rectalcancer by contact (endocavitary) irradiation. Diseases of the Colon &Rectum, 30(11), 835-8.

[0343] 33. Leung, J. T., & Kuan, R. (1995). Brachytherapy in oesophagealcarcinoma. Australasian Radiology, 39(4), 375-8.

[0344] 34. Rosenshein, N. B. (1983). Radioisotopes in the treatment ofovarian cancer. Clinics in Obstertrics & Gynecology, 10(2), 279-95.

[0345] 35. Volterrani, F., Prosperini, G., Sigurta, D., Vona, S.,Musumeci, R., Milani, A., & Luciani, L. (1979). Present status oftreatment for invasive cervical carcinoma. Tumori, 65(5), 611-24.

[0346] 36. Spencer, R. P., Nuclear medicine and therapy: a reorientationto specificity and beta ray generators, Symposium on Therapy in NuclearMedicine, 3-15, (1978).

[0347] 37. Knapp, F. F., Callahan, A. P., Beets, A. L., Mirxadeh, S.,and Hsieh, B. T., Processing of reactor-produced ¹⁸⁸W for fabrication ofclinical scale alumina-based ¹⁸⁸W/¹⁸⁸Re generators, Appl. Radiat. Isot.,45:1123-1128 (1994).

[0348] 38. Johns, H. E., and Cunningham, J. R. The Physics of Radiology(4th Edition). Charles Thomas, Publisher (Springfield, Ill., 1983).

[0349] 39. Berger, M. J. and Seltzer, S. M., Stopping powers and rangesof electrons and positrons, 2nd ed., U.S. Dept. Of Commerce PublicationsNBSIR 82-2550-A, (1983).

[0350] 40. Friedell, H. L., Thomas, C. I., and Krohmer, J. S.Description of an Sr⁹⁰ beta-ray applicator and its use on the eye. Amer.J. Roentg. 65, 232-245 (1951).

[0351] 41. Simpkin, D. J. and Mackie, T. R., EGS Monte Carlodetermination of the beta dose kernel in water, Med. Phys., 17:179-186(1990).

[0352] 42. McLaughlin, W. L, Chen. Y. D, Soares, C. G., Miller, A.,VanDyck, G., and Lewis, D. F., Sensitometry of the response of a newradiochromic film dosimeter to gamma radiation and electron beams, Nucl.Instrum. Meth. Phys. Res., A 302:165-176 (1991).

[0353] 43. Berger, M. J., Distribution of absorbed dose around pointsources of electrons and beta particles in water and other media, MIRDPamphlet No. 7, J. Nucl. Med. 12, Suppl. No. 5, 5-24 (1971).

What is claimed is:
 1. A dual-balloon catheter for treating a diseaseprocess in a luminal structure of a patient, comprising: an innerballoon; an outer ballon substantially concentric with and substantiallysurounding the inner ballon; an inner balloon fluid delivery lumen influid connection with the inner balloon; and an outer balloon fluiddeliverly lumen in fluid connection with the outer balloon.
 2. Thecatheter of claim 1 , further comprising a guidewire lumen connected toan outer surface of said outer balloon.
 3. The catheter of claim 2 ,wherein the inner balloon fluid delivery lumen, the outer balloon fluiddelivey lumen, and the guidewire lumen are in substantially axialalignment.
 4. The catheter of claim 1 , further comprising a guidewirelumen extending through the outer balloon.
 5. The catheter of claim 4 ,wherein the inner balloon fluid delivery lumen, the outer balloon fluiddelivey lumen, and the guidewire lumen are in substantially axialalignment.
 6. The catheter of claim 1 , further comprising a guidewirelumen extending through the outer balloon and the inner balloon.
 7. Thecatheter of claim 6 , wherein the inner balloon fluid delivery lumen,the outer balloon fluid delivey lumen, and the guidewire lumen are insubstantially axial alignment.
 8. The catheter of claim 1 , wherein theinner balloon has a radiation producing coating.
 9. The catheter ofclaim 1 , wherein the outer balloon has a radiation producing coating.10. A method for treating a disease process in a luminal structure of apatient, comprising: insering into the luminal structure a dual-ballooncatheter including an inner balloon, an outer ballon substantiallyconcentric with and substantially surounding the inner ballon, an innerballoon fluid delivery lumen in fluid connection with the inner balloon,and an outer balloon fluid deliverly lumen in fluid connection with theouter balloon; and inserting a radioactive fluid into at least one ofthe inner ballon and the outer balloon through the inner balloon fluiddelivery lumen and the outer balloon fluid delivery lumen, respectively.11. An indiflator for inserting fluid into a balloon catheter,comprising: an elongated tube for holding the fluid, the elongated tubehaving a first end and a second end; the first end of the elongated tubehaving a wall accross the tube with a port therein for providing a fluidpassage between an interior of the tube and an exterior of the tube; aplunger assembly including a plunger head with a first face and a secondface and a plunger stem having first and second ends; the plunger headbeing adapted to slide within the tube and being connected at the firstface to the first end of the plunger stem; lock means disposed at thesecond end of the tube for accepting and releasably locking the plungerstem, the second end of the plunger stem being disposed outside thetube; and a pressure valve disposed adjacent the second end of theplunger stem and being operatively connected to a pressure transucer onthe second face of the plunger head facing the first end of the tube,whereby the pressure valve displays a pressure in an area of the tubebetween the first end of the tube and the second face of the plungerhead.
 12. The indiflator of claim 11 , wherein said area of the tubebetween the first end of the tube and the second face of the plungerhead is substantially transparent and is calibrated to indicate thevolume between the first end of the tube and the second face of theplunger head.
 13. The indiflator of claim 12 , wherein the calibrationis between about 1 and 5 cc's and is in increments of about 0.1 cc.